The mechanical properties of these films were also improved when compared with films produced without CO. Conversely, the water barrier properties of composite films decreased (p < 0.05) when the concentration of gelatin in composite films increased. Comparing with pure gelatin films, water and oxygen barrier properties of gelatin films decreased when manufactured with the inclusion of CO.The objectives of this study were to develop composite films using various gelatin sources with corn oil (CO) incorporation (55.18%) and to investigate the mechanical and physical properties of these films as potential packaging films. There were increases ( Biopolymers, based on carbohydrates and proteins, have been extensively studied to develop edible/biodegradable films with more versatile properties . HoweverGenerally, protein-based films offer better mechanical and barrier properties than those manufactured from polysaccharides . This iset al. [In addition to lipid incorporation, altering the pH of film-forming solutions may also be one of the many approaches required to improve functional properties of biopolymer films ,22,23,24et al. , higher et al. [et al. [In our previous study , films met al. ), and co [et al. .Beef skin gelatin (Bloom 220), pork skin gelatin (Bloom 225) and fish skin gelatin from warm water Tilapia (Bloom 240) were purchased from Healan Ingredients Ltd. . Corn oil and glycerol were obtained from Sigma Aldrich Co. . For pH adjustment, NaOH was obtained in pellet form and lactic acid was obtained from Merck  and May & Baker Ltd. , respectively.et al. [et al. [Gelatin powders were solubilised in distilled water at concentrations between 4%–8% (w/v). Glycerol was added as a plasticizer at a constant glycerol/gelatin powder ratio of 2:5 (w/w). Corn oil (CO) was introduced into all gelatin solutions at a set concentration of 55.18% (w/w), in accordance with those recommendations proposed by Wang et al. . Dispers [et al. . All solScanning electron microscopy (SEM) was used to investigate the morphology of the films using JSM-5510  at 5.0 kV. Film samples were cut into appropriate-sized samples and mounted on stubs using double-sided adhesive tape. Prior to analysis, films were coated with gold to make the samples conductive. Subsequently, samples were observed at 1000× magnification.Film thickness was measured using a hand-held digital micrometer . Measurements were carried out at different film locations and the mean thickness value was used to calculate the permeability of the films.L = 97.79, a = 5.18, b = 7.91) and Hunter L, a and b colour values were measured. Colour coordinates ranged from L = 0 (black) to L = 100 (white), −a (greeness) to +a (redness), and −b (blueness) to +b (yellowness).The surface colour of gelatin films was measured using a Minolta chromameter . Gelatin films were placed on the surface of a white standard plate , set at a wavelength of 500 nm. Four film specimens were taken from each film sample and cut into rectangular pieces (45 × 10 mm). The sample was placed on the inner side of a transparent plastic 10 mm cuvette and the absorbance measured.et al. [The opacities of films were calculated by the following equation according to the method described by Gontard et al. :opacityThe mechanical properties of films were evaluated and included; tensile strength (TS), elongation at break (EAB) and puncture strength (PS) using an Imperial 2500 Mecmesin force and torque tester  according to the ASTM-D882 . TS of aWater vapour permeability (WVP) was calculated from the following equation:et al. [et al. [WVP of gelatin films was measured according to the WVP correction method of McHugh et al.  which iset al.  for dete [et al. . Distillet al. [3·μm/m2·day·kPa); S = slope indicating the transmission rate of oxygen; β = permeability coefficient (4.776), a constant value as all treatments were conducted at the same conditions; A = surface area of the film (m2); T = thickness of the test film samples (μm); V = volume of the chamber (mL).Oxygen permeability was conducted according to the method developed by Papkovsky  and Wanget al. . An oxygThe film solubility was determined according to the method of Gontard and Guilbert  by trimm−1 with automatic signal gain collected in 32 scans with a resolution of 4 cm−1 that were rationed against a background spectrum. Four replicate spectra were obtained and the average spectrum was taken for analysis. The IR spectra for gelatin films were determined using a Varian 600-IR Series FTIR  equipped with horizontal attenuated total reflectance (ATR) ZnSe cell at room temperature. The detector used was a Deuterated Tri-Glycine Sulfate (DTGS-KBR). Before film analysis, a background spectrum using a clean crystal cell was recorded. Films were placed onto the crystal cell and the cell was clamped into position on the FTIR spectrometer. FTIR spectra were recorded in the range of 500–4000 cmp < 0.05 were considered to be significant. Differences between means were compared using Duncan’s multiple range test method.Statistical analyses were performed using one-way analysis of the variance (ANOVA) and the LSD test (least significant difference) which showed the statistically different values. Statgraphics Centurion XV software programme  was used with differences at The surface micrographs obtained by SEM are shown in p < 0.05) when gelatin concentrations of 6% and 8% were utilized  the L values, with films derived from pork gelatin sources possessing the highest L value. Results also indicated that increasing the concentration of gelatin decreased (p < 0.05) the L value of composite films manufactured from gelatin derived from beef sources. Composite films derived from beef gelatin sources also had lower (p < 0.05) a values compared to those derived from pork and fish gelatin sources.The colour attributes of gelatin composite films derived from beef, pork and fish sources are presented in b values. However, composite films derived from beef gelatin sources possessed higher (p < 0.05) b values. This was most probably due to the base colour of beef gelatin powder which possessed a yellowish hue compared to the other gelatin powder sources. The results obtained also indicated a decrease in L and a values for all composite films when compared with gelatin films manufactured without the use of CO [b values for all gelatin composite films were higher compared to those gelatin films manufactured by Nur Hanani et al. [Additionally, composite films manufactured using pork- and fish-derived gelatins did not significantly show differences in se of CO , regardli et al.  which dip < 0.05) opaqueness for all gelatin-based composite films  affected by gelatin source, particularly at concentrations of 6% and 8%, for example, composite films manufactured from beef gelatin at 6% and 8% possessed the lowest TS values of all composite films manufactured. The increased concentration of gelatin also increased (p < 0.05) the TS values of composite films derived from pork and fish gelatin sources with fish gelatin employed at an 8% concentration showing the highest TS value (11.14 MPa). This trend was also observed for all composite films when the EAB test was conducted. Differences in EAB values for all composite films were significantly (p < 0.05) dependent on the concentration of gelatin used, especially for those derived from beef gelatin. With respect to PS, composite films manufactured from gelatin derived from beef sources had the lowest PS value, regardless of the gelatin concentration used. The results also showed that no significant differences in PS values were found between composite films manufactured from gelatin derived from pork and fish sources. Statistical analysis also showed that increasing the concentration of gelatin increased (p < 0.05) the PS values of all gelatin composite films. The mechanical properties of gelatin composite films are shown in When the composite films produced in this study were compared with pure gelatin films , resultsp < 0.05) WVP values than composite films derived from fish gelatin sources. The results also demonstrated that increasing gelatin concentration from 4% to 8% increased (p < 0.05) the WVP values of all gelatin-based composite films. According to Nur Hanani et al. [et al. [et al. [The WVP of gelatin-based composite films incorporating CO is shown in i et al.  and Hoqu [et al. , some ge [et al. , it was  [et al. .et al. [According to Bertan et al. , adding et al. ,6. The lp < 0.05) higher compared to films derived from beef and pork gelatin sources. Overall, increasing the concentration of gelatin in films increased (p < 0.05) OP. When the composite films manufactured in this study were compared with pure gelatin films [Oxygen permeability of gelatin composite films is presented in in films  it was oet al. [The increased OP observed in composite films may in fact be related to the significant presence of CO (highest concentration of oil use in such films to date) and the hydrophobic nature of this lipid component, consequently facilitating oxygen transfer ,6,37,38.et al. , in spitp < 0.05) in film water solubility values for composite films derived from fish gelatin. However, these films had the lowest solubility values when compared to composite films derived from beef and pork gelatin sources, regardless of concentration used. At a gelatin concentration of 4%, no significant differences in the water solubility of composite films were determined between those formed from both beef and pork gelatin. When compared with the pure gelatin films [p < 0.05) in the water solubility of the films particularly for composite films derived from pork and fish gelatin sources. According to the scientific literature, Gontard et al. [et al. [et al. [The solubility of gelatin-based composite films is presented in in films , the addd et al.  and Bert [et al.  obtained [et al.  observedHowever, contrary results were obtained for composite films manufactured from gelatin derived from beef sources. At a 6% gelatin concentration, films derived from beef gelatin sources had the highest water solubility. This was most likely due to the presence of lactic acid usage which was added during the preparation of the solution to control the pH at 10.54. During the preparation of film forming solutions, lactic acid had been used in the solutions of beef gelatin sources at 6% concentration to adjust the pH value. Lactic acid is hygroscopic, therefore it had attracted and held water molecules and encourage solubility of film in water.−1 correspond to amide-A and water molecules, amide I, amide II, and amide III, respectively [2 groups of glycine [FTIR analysis was carried out on all composite films . The absectively ,42,43. A glycine ,42,43.−1 is the most useful peak for infrared analysis of secondary protein structures like gelatin [et al. [et al. [−1 is characteristic for the coil structure of gelatin. Increasing gelatin concentrations, particularly for films manufactured from gelatin derived from pork and fish sources, shifted the amide I peak to a higher wavenumber. The change in amide I band for gelatin films suggested that CO might affect the helix coil structure of gelatin films as suggested by Jongjarenrak et al. [Among these absorption bands, the amide I band between 1600 and 1700 cm gelatin ,45. Jong [et al.  and Yaki [et al.  reportedk et al. . These a−1. The peaks around 2925 and 2854 cm–1 are related with the symmetric and asymmetric stretching vibration of the aliphatic group (CH2) [−1 also appeared and indicated strong C = O absorption from the oil. Composite films manufactured from gelatin derived from beef sources with 6% concentration displayed a higher wavenumber of 1116 cm−1 compared with other gelatin films. The peak shift is most likely due to the presence of lactic acid which was used during the preparation of the solution to standardize pH solution values. This spectrum supports previously described results, for example, the increased solubility of composite beef gelatin derived films due to the presence of lactic acid.The FTIR spectra of the films also showed some interactions occurred between gelatin and CO as indicated by the presence of a high peak in the frequency range between 2500 and 3100 cmup (CH2) ,47. Meanet al. [Experimental studies were conducted and based on the proposed model for optimum gelatin-based composite film manufacture as outlined by Wang et al. . This mo


A substantial proportion of the burden of depression arises from its recurrent nature. The risk of relapse after antidepressant medication (ADM) discontinuation is high but not uniform. Predictors of individual relapse risk after antidepressant discontinuation could help to guide treatment and mitigate the long-term course of depression. We conducted a systematic literature search in PubMed to identify relapse predictors using the search terms ‘(depress* OR MDD*) AND (relapse* OR recurren*) AND (predict* OR risk) AND (discontinu* OR withdraw* OR maintenance OR maintain or continu*) AND (antidepress* OR medication OR drug)’ for published studies until November 2014. Studies investigating predictors of relapse in patients aged between 18 and 65 years with a main diagnosis of major depressive disorder (MDD), who remitted from a depressive episode while treated with ADM and were followed up for at least 6 months to assess relapse after part of the sample discontinued their ADM, were included in the review. Although relevant information is present in many studies, only 13 studies based on nine separate samples investigated predictors for relapse after ADM discontinuation. There are multiple promising predictors, including markers of true treatment response and the number of prior episodes. However, the existing evidence is weak and there are no established, validated markers of individual relapse risk after antidepressant cessation. There is little evidence to guide discontinuation decisions in an individualized manner beyond overall recurrence risk. Thus, there is a pressing need to investigate neurobiological markers of individual relapse risk, focusing on treatment discontinuation. Notably, although such high-risk patients are typically prime targets for treatment, they would derive as little advantage from the medication as those who will not relapse either way.Hence, it is critical to establish predictors of the relapse risk for individual patients. In terms of clinical guidance, this raises two related questions. The first asks what the individual's relapse risk would be after discontinuation. Patients who have a very low risk of relapse after discontinuation have less scope for benefiting from further treatment  AND (relapse* OR recurren*) AND (predict* OR risk) AND (discontinu* OR withdraw* OR maintenance OR maintain or continu*) AND (antidepress* OR medication OR drug)’ for published studies until November 2014. The search resulted in 899 retrieved studies.a);f) and unclear cases discussed jointly. Authors of individual studies were not contacted.I.M.B. and Q.J.M.H. first screened all titles. Abstracts of all titles judged potentially relevant by either author were then judged on inclusion criteria et al.Of note, the natural course of depressive episodes suggests that re-emergence of symptoms within 6–9 months might be due to relapses into the index episode while thereafter they indicate a new episode  failed to reach significance in three studies , there was no discontinuation effect in the minority groups. However, power in these groups was low .One study investigated the effect of race and ethnicity . Although the drug–placebo difference in prophylactic efficacy was higher for patients with recurrent depression (i.e. 31% v. 11%), the treatment × prior episode events interaction analysis did not significantly predict time to re-emergence (p = 0.25), possibly due to power issues .Of note, in the study by Keller et al.  the risket al.et al.et al.Only two studies report examining an interaction of severity at onset with treatment, both failing to reach significance . Though these results are suggestive, neither study explicitly tested for interactions. McGrath et al.  after milnacipram discontinuation. Analyses in a further study investigating specific residual symptoms, namely phobic anxiety, also failed to yield significant results  and symptoms emerging with treatment . This effect was absent in patients with a non-specific response to treatment and in those with atypical vegetative symptoms. The interaction of treatment and neurovegetative symptoms alone was not reported by McGrath et al. . However, no interaction was reported and the effect did not survive when controlling for neurovegetative pattern , even though melancholic and neurovegetative patterns were uncorrelated. Melancholic subtype did not interact significantly with treatment in the study by McGrath et al. , but not in the continuation group, though no interaction was reported. Relapse rates were 28.5% v. 27.2% and 53.3% v. 40.7% for continuation and discontinuation groups with high and low anxiety, respectively. Fava et al. .Somatic pain ratings were found to interact significant with treatment in one study on duloxetine (Fava Other variables investigated only once and not found to interact with treatment are presented in et al.et al.et al.et al.et al.Many of the factors reported on here appear to have robust properties as predictors of relapse or recurrence risk independent of medication discontinuation: number of previous episodes (Berlanga et al.However, the relevant question for the individual patient really is about the differential impact of medication: will this particular person benefit from continuing treatment? This requires understanding and predicting not just overall relapse risk, but the specific consequences of medication discontinuation, i.e. effects within the separate arms. Although people with a high risk of relapse have more scope to benefit from maintenance treatment, they may still not respond and therefore not benefit. In addition, discontinuation itself is likely to have an effect on relapse, indicated by the increased risk in the early months following discontinuation, which is independent of length of prior treatment (Viguera Strikingly, our systematic review identified only 13 studies examining the latter, based on only nine datasets. This is thus very poorly understood even though data relevant to this question are routinely available in studies examining continuation and maintenance treatment of depression.et al.et al.et al.et al.et al.et al.et al.et al. (et al.Overall, the state of the field is insufficient to draw either positive or negative conclusions. Nevertheless, a few findings are noteworthy. First, guidelines typically recommend continuation treatment for around 4–9 months (Bauer .et al.  found to. et al. found anet al. (et al. (et al. (Second, the reviewed studies individually failed to show clear effects of prior episode number. Two meta-analyses have addressed this, with discrepant results. While Viguera et al.  found th (et al.  came to  (et al.  found noet al.et al.et al.et al.et al.et al.Third, the studies have also not provided clear support for the influence of residual symptoms. This is again surprising. Residual symptom load affects relapse risk overall (Nierenberg et al. (et al. (et al.The studies by Stewart et al.  and Nier (et al.  both sho. et al., this rapost-hoc comparisons between subgroups correcting for multiple comparisons to identify subgroup difference that gave rise to the significant interaction term. Few studies followed this approach, typically either not reporting the interaction term, or, if the interaction term is reported to be significant, not doing sufficient post-hoc comparisons to establish what gave rise to the significant interaction term. Furthermore, corrections for multiple comparisons were not consistently reported.Methodologically, to establish the effect of risk reduction after discontinuation of a certain predictor and whether a subgroup identified by the predictor would not benefit from continuous ADM treatment, one would ideally first compute the significance level of the interaction of treatment and predictor and, only if significance is reached, do et al.et al.et al.et al.a priori to benefit from continuation treatment. If treatments are encapsulated, blinding may be partially broken if capsules are intentionally or unintentionally opened and the true drug/placebo identified. This may artificially increase drug–placebo relapse rates and thereby reduce the impact of moderators. Andrews et al. (One possibility for the lack of significant findings is that antidepressant discontinuation has a far stronger effect on relapse rates than any other variable, and that only very large studies or meta/mega-analyses could identify the smaller moderating factors. The strength of the effects for instance of number of prior episodes reported in two meta-analyses (Viguera s et al.  identifiet al.et al. (The present systematic review has some limitations. First, since we only used one database for our search and the database had not access to the full text of all relevant studies for the search, it is possible that we missed eligible studies. There may also be a positive bias due to reporting biases, as positive findings were more likely to be cited in the reviews of which we examined, and as they are more likely to form part of the title of the paper which we based our initial search on. We did not formally evaluate the quality of the included studies as the results were overall weak. A second drawback of the review is the fact that we excluded studies that investigated the effect of psychotherapy on relapse risk after antidepressant discontinuation as this would have confounded the findings given that psychotherapy is known to be effective in preventing relapses (e.g. Hollon .et al. . In factet al.et al.v. discontinuation. On the one hand, this is clearly due to the scarcity of studies that have attended to the problem. On the other hand, the strong effects on relapse rates of both antidepressants and predictors would have rendered strong interaction effects a distinct possibility. It is hence critical to revisit the existing datasets to re-examine this problem. In doing so, the field can now avail itself of novel techniques both from machine learning and computational psychiatry (Huys et al.et al.et al.et al.Maintenance treatment after a remission from depression, particularly after multiple episodes, is the standard of care. However, it is not a panacea. Patients discontinue for a variety of reasons including side effects; and there are indications that tachyphylaxis (Rothschild et al. (et al. (Finally, the list of predictors evaluated so far includes no neurobiological assessments. This should be addressed as such measurements hold great promise in predicting individual outcomes. Farb et al. , for ins (et al.  found th


Have we not uncovered any new findings that would make exercise prescription more efficient and overcome many of the purported barriers to participation? Is there no evidence to help health professionals to adequately choose and design exercise program for specific outcomes?We are pleased to present this special issue. As we noted in our call for papers for this special issue,Physical inactivity is considered one of the most important public health problems of the 21st century  and incrIt is important to recognize that the positive effects of exercise are null if people do not engage with it and if the programs engaged with do not produce improvements in the desired outcomes , 9. In tContributions from A. Wittke et al., W. D. N. Santos et al., and J. Steele et al. have considered applications of resistance training exercise in both healthy  and diseased populations (breast cancer survivors). They have provided insight into the applications of resistance training (application of progressive high effort), its effects in combination with supplementation (protein), and both the positive outcomes and risk of adverse effects in a clinical population (breast cancer survivors).Work from C. Ranucci et al., T. Dalager et al., and L. Fox et al. have also offered insights into “real world” multidisciplinary approaches to exercise. C. Ranucci et al. report the positive effects of a family-based multidisciplinary approach to improving health status, nutrition habits, and physical performance in overweight and obese children or adolescents. T. Dalager et al. showed the implementation of “Intelligent Physical Exercise Training” compared with moderate intensity physical activity on a workplace setting upon musculoskeletal health. Further, L. Fox et al. provide important “real world evidence” on quantitative and qualitative data feedback from men with prostate cancer who had undergone a structured exercise intervention.Lastly, S. C. E. Schmidt et al. report on the results of an important 18-year longitudinal study examining the effects of physical activity types, fitness, and health in adults. They report key findings regarding the role of type of physical activity upon fitness and health, as well as the impact of confounding sociodemographic factors.We hope that the contributions from authors in this special issue serve to aid in enhancing specific exercise prescription in a range of populations and that they also stimulate further interest and work in advancing our understanding of exercise in both health and disease.Paulo GentilFabrício Boscolo Del VecchioJames Steele


In this paper, we study the complete convergence and complete moment convergence for weighted sums of extended negatively dependent (END) random variables under sub-linear expectations space with the condition of  Additivity has been generally regarded as a fairly natural assumption, so the classical probability theorems have always been considered under additive probabilities and the linear expectations. However, many uncertain phenomena do not satisfy this assumption. So Peng –5 introdSub-linear expectations generate lots of interesting properties which are unlike those in linear expectations, and the issues in sub-linear expectations are more challenging, so lots of scholars have attached importance to them. Numbers of results have been established, for example, Peng –5 gainedby Zhang –9. He alby Zhang  also resby Zhang  studied et al. [et al. [et al. [et al. [The complete convergence has a relatively complete development in probability limit theory. The notion of complete convergence was raised by Hsu and Robbins , and Choet al. , Wang et [et al.  and Wu a [et al. , and so  [et al.  gained g [et al.  research [et al.  under suIn the next section, we generally introduce some basic notations and concepts, related properties under sub-linear expectations and preliminary lemmas that are useful to prove the main theorems. In Section The study of this paper uses the framework and notations which are established by Peng –5. So, wn-dimensional random vectors defined severally in the sub-linear expectation space  Assume that a space (ii)(Extended negatively dependent) A sequence of random variables ε̂.It is distinct that if C is on behalf of a generic positive constant which may differ from one place to another. Let n, n.In the following, let The following three lemmas are needed in the proofs of our theorems.is a slow varying function if and only ifwhereandSupposeandis a slow varying function. (i)Then, for(ii)Ifthen for anyand(i) By Lemma equality , and \do(ii) By the proof of (i), we can imply that for any . By , we can  that by , \documeCase 2: By , we can n large enough,By  and \docBy Definition n))2. By , we have that by \documen}I32. By , we can This finishes the proof of Theorem Without loss of generality, we can assume that Case 1: n, there exists k such that Note  and 4.44.4, whicproof of . Next, w thus by , 4.13),,4.13\doc that by , \documeCase 2: n large enough,By We use the same notations as those in Theorem her with  yields t


A multi-model X-ray imaging approach was implemented to probe the interaction of nanomaterials with a mammalian cell in three dimensions. With further developments, this approach could have an impact on nanomedicine and nanotoxicology. The scope of their application has also broadened dramatically. With this comes an increase in the possibility of human exposure to such materials and several of their properties give cause for concern 22 nanoparticles, a promising antitumour agent. Dual-energy scanning transmission X-ray microscopy (STXM) was used to image a whole macrophage at different sample orientations , they acquired two tomographic tilt series by rotating the sample around a single axis. Each tilt series consists of 46 images with a tilt range of ±79.4°.In this issue of et al., 2005i.e. the electron density of the sample cannot be negative) and a loose support . In reciprocal space, the measured data are used as the constraint in each iteration. After several hundreds of iterations, the algorithm converges to a global solution that is consistent with the measured data and physical constraints. It has been experimentally demonstrated that EST not only produces superior results to other traditional tomographic algorithms, but also is broadly applicable to three-dimensional imaging of biological and physical samples, ranging from breast tumors and cellular structures to single atoms in materials  (Miao a) shows the three-dimensional volume rendering of the reconstructed macrophage with the Gd@C82(OH)22 nanoparticles in dark red, the nucleus in brown and different types of lysosomes in yellow. The three-dimensional reconstruction provides more faithful cellular structure information than the two-dimensional projection image . Furthermore, by subtracting the two reconstructions measured above and below the Gd absorption edge, the three-dimensional distribution of the nanoparticles inside the macrophage was obtained . They found that nanoparticles were mainly aggregated in lysosomes and no nanoparticles were distributed in the nucleus. These observations were further corroborated by the X-ray fluorescence microscopy image of the same macrophage .By combining dual-energy STXM and EST, Jiang and collaborators reconstructed the macrophage structure with a three-dimensional resolution of 75–80 nm. Fig. 1ge Fig. 1b. Furthed Fig. 1c. They ge Fig. 1d.et al., 1999et al., 2007et al., 2008et al., 2017et al., 1995et al., 2015et al., 2017et al., 2017et al., 2017et al., 2015Looking forward, several additional developments could make this multi-model imaging approach widely applicable in nanomedicine and nanotoxicology. First, coherent diffractive imaging (CDI) has to be incorporated to improve the spatial resolution (Miao


Even though mental disorders represent a major public health problem for women and respective children, there remains a lack of epidemiological longitudinal studies to assess the psychological status of women throughout pregnancy and later in life. This epidemiological cohort study assessed the relationship between mental disorders of 409 Brazilian women in pregnancy and 5–8 years after delivery.per capita income, family size, work, marital status and body mass index.The women were followed from 1997 to 2000 at 17 health services, and subsequently from 2004 to 2006 at their homes. Mental disorders were investigated by the Perceived Stress Scale-PSS, General Health Questionnaire-GHQ and State-Trait Anxiety Inventories-STAI. The relationship between scores of the PSS, GHQ and STAI 5–8 years after delivery and in pregnancy was assessed by multivariate linear regression analysis, controlling for the following confounders: maternal age, education, per capita income (adj. R2 varied from 0.15 to 0.37). PSS, GHQ and STAI scores in the 3rd trimester of pregnancy were positively associated with scores of the PSS, GHQ and STAI in the 1st and 2nd trimesters of pregnancy (adj. R2 varied from 0.31 to 0.65).Scores of the PSS, GHQ and STAI 5–8 years after delivery were positively associated with scores of the PSS, GHQ and STAI in the three trimesters of pregnancy, and inversely associated with maternal age and The results of this study reinforce the urgency to integrate mental health screening into routine primary care for pregnant and postpartum women. Women with chronic infectious diseases, metabolic diseases, cardiopathy, mental diseases, hypertension/pre-eclampsia/eclampsia, vaginal bleeding and multiple deliveries were excluded from the study. Details of the cohort have been published previously , with a precision of 100 g. Height was measured with a SECA® wall-mounted stadiometer , with a precision of 0.1 cm. The anthropometric measurements were performed according to the recommendations of Jelliffe & Jelliffe  and classified according to WHO recommendations WHO, . The womJelliffe .et al.  and 5–8 years after delivery, using versions of the Perceived Stress Scale (PSS), the General Health Questionnaire (GHQ) and the State-Trait Anxiety Inventories (STAI) validated in Brazil, respectively, by Luft et al. , Mari & et al.  and Biag  was used for storage and statistical analysis of the data. The relationship between scores of the PSS, GHQ and STAI 5–8 years postpartum (dependent variables) and in the three trimesters of pregnancy (independent variables) was assessed by multivariate linear regression analysis, using the backward stepwise selection method. The relationship between scores of the PSS, GHQ and STAI in the 3rd trimester of pregnancy (dependent variables) and in the 1st and 2nd trimesters (independent variables) was also assessed. The following confounding factors were included in the models: maternal age, education, n = 745) in the first phase of the study, and the ones who participated in the original cohort (n = 865). Comparison of the characteristics between the mothers included in the cohort and those who did not conclude the study showed no significant differences.There were losses of 33.6% and 42.7% of the sample, respectively, considering all the mothers who were located (per capita income (adj. R2 = 0.21). Scores of the GHQ 5–8 years after delivery were positively associated with scores of the GHQ in the three trimesters of pregnancy, and inversely associated with maternal age and per capita income (adj. R2 = 0.18). Scores of the SAI 5–8 years after delivery were positively associated with scores of the SAI in the 2nd and 3rd trimesters of pregnancy, and inversely associated with per capita income (adj. R2 = 0.15). Scores of the TAI 5–8 years after delivery were positively associated with scores of the TAI in the 1st and 2nd trimesters of pregnancy, and inversely associated with maternal age and per capita income (adj. R2 = 0.37).R2 varied from 0.31 to 0.65).per capita income and mental disorders 5–8 years after delivery. The other socioeconomic and demographic factors investigated did not show statistically significant results. BMI, an indicator of the nutritional status of the women, was not associated with mental disorders; though Nagl et al.  in the three trimesters of pregnancy, lower age and l et al.  and Moly  5–8 years after delivery compared with the mean scores in pregnancy, while the GHQ, SAI and TAI scores maintained the mean values in the four different periods investigated, indicating higher levels of perceived stress 5–8 years after delivery than in pregnancy. Schmied et al. (et al. (et al. (Comparing the mean scores of the women in the highest PSS tertile with the mean scores of the whole population, and the mean scores of the populations studied by Cohen et al. , we concd et al.  observed (et al.  did not  (et al.  found thet al.et al.per capita income (Abdollahi et al.et al.et al.et al. (et al. (et al. (Similar to other studies in the literature, lower age (Bottino .et al. , materna (et al.  referred (et al. . In fact (et al.  showed tet al. (et al. (et al. (Abdollahi et al.  identifi (et al.  conclude (et al. , using aet al. (A limitation of this study was the lack of assessment of mental disorders in the immediate post-partum period. Even though mental disorders had not been investigated in the immediate postpartum period, it was probably a problem for those pregnant women considering the associations of the PSS, GHQ and STAI scores between the 3rd and 1st and 2nd trimesters of pregnancy. Witt et al.  referredper capita income are associated with mental disorders 5–8 years after delivery.Mental disorders in the three trimesters of pregnancy, lower age and Referral of young, low-income pregnant women with mental disorders, particularly anxiety and depression, should be encouraged to psychological or psychiatric treatment. Finally, we reinforce the urgency to integrate mental health screening into routine primary care for pregnant and postpartum women.


Magnetic nanoparticles are a highly valuable substrate for the attachment of homogeneous inorganic and organic containing catalysts. This review deals with the very recent main advances in the development of various nanocatalytic systems by the immobilisation of homogeneous catalysts onto magnetic nanoparticles. We discuss magnetic core shell nanostructures  as substrates for catalyst immobilisation. Then we consider magnetic nanoparticles bound to inorganic catalytic mesoporous structures as well as metal organic frameworks. Binding of catalytically active small organic molecules and polymers are also reviewed. After that we briefly deliberate on the binding of enzymes to magnetic nanocomposites and the corresponding enzymatic catalysis. Finally, we draw conclusions and present a future outlook for the further development of new catalytic systems which are immobilised onto magnetic nanoparticles. Catalysts play a very important role in modern science and technology as they improve reaction yields, reduce temperatures of chemical processes and promote specific enantioselectivity in asymmetric synthesis. There are two main types of catalysis, heterogeneous, where the catalyst is in the solid phase with the reaction occurring on the surface and homogeneous, where the catalyst is in the same phase as the reactants . Both prThe bridge between heterogeneous and homogeneous catalysts can be achieved through the use of nanoparticles . NanoparOne particularly useful and important group of nanoparticles is magnetic nanoparticles (MNPs). These nanoparticles may be composed of a series of materials such as metals like cobalt and nickel, alloys like iron/platinum and metal oxides like iron oxides , and ferIn addition to all the above, magnetic nanoparticles can serve as a highly useful catalyst support enabling immobilization and magnetic recovery of the catalyst . In the 2 [Several types of magnetic nanostructures have developed for the use of catalysis ,18, incl2  as well 2 . These n2  and phot2 . In addi2 .sec-alcohols with synthetically useful selectivity under ambient temperature, low catalyst loading, and using acetic anhydride as the acylating agent. The use of this catalyst enabled the isolation of resolved alcohols with good to excellent enantiomeric excess. Most importantly, the interaction between the nanoparticle core and the organocatalyst unit results in a chiral heterogeneous catalyst which is recyclable to an unprecedented extent—32 times consecutive cycles—while retaining high activity and enantiomeric selectivity profiles [Another type of catalyst which is of interest for organic synthesis involves the use of organic molecules. These molecules show a large degree of specificity for their reactions and may allow a more successful reaction than conventional chemistry. There are two types which may potentially be used for the purposes of organic reactions, there are metal complexes which may be used to generate chemical reactions through oxidation state changes in the metal centre as well as organocatalysts which contain no metal centre and utilise conformational changes to initiate the reaction. While the metal centres may be in certain instances toxic the organocatalysts are not, but may be synthetically complex to produce, and as a result in both cases it is also desirable to retain these catalysts after use for recycling. For example, it was reported that “hypernucleophilic” 4-N,N-dimethylaminopyridine (DMAP) catalyst immobilised on magnetite nanoparticles was very active and recyclable in acyl transfer processes, Stieglitz rearrangements and hydroalkoxylation reactions at loadings between 1% and 10% and could be recovered and recycled over 30 times without any discernible loss of activity . In anotprofiles .Overall, the binding of catalysts to magnetic nanoparticles allows the retention of these materials after the end of the reaction for reuse. This will prevent the necessity of additional purification techniques to remove the catalyst from the waste stream making it a “greener” catalyst comparing to previous approaches. This area has deserved a lot of attention and there have been several good reviews on the subject of catalysts immobilised onto magnetic nanoparticles ,27,28,30et al. [3O4 nanoparticles can be reused up to five times with good yield. Pericàs et al. [et al. [Over the last few years significant progress was made in the development of new inorganic catalytic systems which are immobilized onto magnetic nano-carriers. Normally, to protect magnetic core and retain magnetic properties the core is coated with some non-magnetic relatively inert shell such as silica. The silica shell is very easy to be functionalized and good for binding of various catalytic species including transition metal complexes. As reported by Astruc et al.  ruthenius et al.  have als [et al.  reportedet al. [Another catalyst was reported by García-Garrido et al.  which inet al. [Esmaeilpour et al.  coated met al.  utilizedet al. [Zolfigol et al.  developeet al. [Kim et al.  publisheet al. reported the immobilization of a palladium species to the surface of cobalt ferrite nanoparticles for the use in Suzuki coupling [et al. [3O4 nanoparticle and then binding to a palladium metal centre. This catalyst was used for the conversion of an alkyne to an alkene with both high yield and selectivity (both >90%).Phan coupling  and for coupling . It was  [et al.  involvinet al. [Nazifi et al.  functionet al. [It was reported by Nakagaki et al.  that maget al. [It was also demonstrated by Naeimi et al.  that broet al. [A silica shell was also utilised by Yoon-Sik Lee et al.  for the et al. [et al. [et al. [3PW12O40 to the surface of silica coated magnetic nanoparticles providing a new catalyst system which has shown good activity in the esterification of free acids in methanol.However, it is not necessary for the silica shell to be inert and this might contribute to the catalysis. For example, it was demonstrated that with limited chemical modification a silica shell can also act as a mesoporous catalyst. Yeung et al.  produced [et al.  reported [et al.  bound thet al. [et al. [3O4 nanoparticles which had been stabilized by poly(N-vinylimidazole). The addition of copper (II) to this polymer iron oxide nanocomposite produced a species that exhibited oxidative catalysis of 2,6-dimethylphenol in water. These species were extracted from the reaction medium with a recovery rate of over 95% and conversion rates of as high as 79.2% with supplementary catalysis.The coating of nanoparticles with polymer shells was also explored in recent years. For example, an interesting catalytic system was reported by Heinze et al. . They us [et al.  reportedet al. [A very interesting approach was reported by Stark et al. . The reset al. [Commercially available polymer encapsulated magnetic beads can also be used to produce new catalytic systems. For example, Kanoh et al.  reportedet al. [3O4@ZIF-8) which were used as catalytic particles for the Knoevenagel reaction in a capillary flow reactor.Remarkable zeolitic framework coated magnetic nanocomposites have been used as catalysts for a flow reaction system. Yeung et al. , designeet al. [Graphitic carbon coated magnetic nanoparticles are also very good materials for further functionalisation in catalysis applications. A highly innovative approach involving the binding of pyrene-tagged dendritic systems  to carboet al. ,55. The The same group has reported the immobilization of hybrid palladium species on a magnetic carbon coated Co nanoparticles using ROM polymerization. This approach has resulted in generation of a magnetically recyclable palladium catalyst for Suzuki-Miyaura cross-coupling reactions . FinallyAs we mentioned, there is a considerable interest in the immobilization of organic catalyst molecules onto heterogeneous substrates. In this case magnetic nanoparticles offer a number of advantages as a substrate enabling the retrieval and recycling of organic catalysts which are normally impossible to remove from the reaction mixture.et al. [3O4 nanoparticles using a triethoxysilane derivative as a linker. The nanocatalysts were applied for the synthesis of biologically active pyrazolophthalazinyl spirooxindoles in high yield  . For exaet al.  bound megh yield . The autet al. [et al. [Ponti et al.  bound an [et al.  the chiret al. [3O4 nanoparticles with an organosilicon linker. This nanocomposite effectively catalyzed the production of β-phosphomalonates from diethyl phosphite and α, β-unsaturated malonates with the added benefit of catalytic action without the danger of noxious fumes from pyridine. The catalyst could also be easily recovered using a magnet and reused at least 10 times without substantial degradation in the activity.Parizi et al.  reportedet al. [In another work Moradi et al.  reportedet al. [An organosilicon linker was also used by Karimi et al.  to bind et al. [Kiasat et al.  used a cet al. [Functional organic polymer coating is also good way to protect magnetic core and functionalise nanoparticles with organic catalytic species. Pericas et al.  describeet al. .et al. [Very interesting magnetic catalytic exchange resins were prepared by Reiser et al.  using poet al. .et al. [Another method for polymer coating of magnetic nanoparticles was reported by Seidi et al.  who usedet al. [There are also reports on direct binding of organic catalytic species to the surface of magnetic iron oxide nanoparticles. For example, functionalised with 4-piperadinecarboxylic acid, magnetite nanoparticles were produced directly via base catalysed precipitation  as reporet al. . These net al. [et al. [Initially, Reiser et al.  developeet al. . More re [et al.  also repet al. [sec-alcohols, the conjugate addition of dimethyl malonate to a nitro-olefin and the desymmetrisation of meso-anhydrides. Despite no physical deterioration of the heterogeneous catalysts being detected on analysis after multiple recycles, in the cases of both the conjugate addition to nitroolefins and the desymmetrisation of meso anhydrides, significant levels of background catalysis by the nanoparticles in the absence of the organocatalyst was detected. This unexpected result clearly demonstrates that magnetite nanoparticle substrates can actually participate in catalytic processes [However, as it was shown by Connon et al. , the uncrocesses .Since nanoparticles are close in size to biomolecules it is likely that they may exhibit some size related properties close to that of the molecules themselves. Enzymes are very active biomolecules, which can serve as highly specific and efficient catalysts. Many enzyme nanomimics which have been produced from nanoparticles showed specific catalytic activities . Enzymeset al. [Candida rugosa stabilised with surfactant. The resulting nanocomposites were then used for the multi-step synthesis of ethyl-isovalerate. Conversion rates of near 80% were reported. It was observed that across a number of catalytic cycles the bound enzyme retained greater catalytic activity than the free enzyme.In one recent work magnetic nanoparticles were produced via precipitation in the presence of gum Arabic by Huizhou et al. . To theset al. [Chitosan stabilised magnetic nanoparticles were used by Kow-Jen Duan et al.  for the et al. [Vali et al.  developeet al. [In similar work by Kim et al.  epoxide et al. [et al. [Yarrowia lipolytica to carbon nanotubes further functionalised with iron oxide nanoparticles. These nanocomposites were shown to be highly effective for the chiral resolution of -1-Phenyl ethanol in heptane. They reported the resistance of the nanocomposites to sonication for up to 30 min.Nanocomposites of carbon nanotubes, amyloglucosidase, and magnetic iron oxides were reported by Goh et al.  that wer [et al.  which inAs we can see from the review above, there are some interesting new developments in catalytic systems immobilised on magnetic nanoparticles. Still there is a clear domination of the standard approach involving silica coating of magnetic iron oxide core followed by functionalisation using appropriate alkoxysilane derivatives. However, very important steps have also been made in the development of various functional polymeric coatings. In addition to mesoporous silica shells, significant progress has also been achieved in the preparation of new mesoporous zeolite-like  and MOF Another interesting development is the immobilization of polydentate dendritic ligands ,55 on maThe report on the background catalytic activity of uncoated magnetite nanoparticles  serves aAnother important aspect is the development of new magnetically immobilised enzymatic catalysts. Despite the number of challenges and difficulties in this field, there is a great potential, particularly for biopharmaceutical applications of enzyme based catalysts.Finally, we think that hyperthermic capabilities of magnetic substrates should be explored in the near future. This field is still very poorly developed despite the great potential opportunities to combine the catalysis with the selective local heating of reagents at the substrate. This should provide significant cost and energy savings, particularly for high temperature catalytic reactions.


Sub-Saharan Africa and other resource-limited settings (RLS) bear the greatest burden of the HIV epidemic globally. Advantageously, the expanding access to antiretroviral therapy (ART) has resulted in increased survival of HIV individuals in the last 2 decades. Data from resource rich settings provide evidence of increased risk of comorbid conditions such as osteoporosis and fragility fractures among HIV-infected populations. We provide the first review of published and presented data synthesizing the current state of knowledge on bone health and HIV in RLS.With few exceptions, we found a high prevalence of low bone mineral density (BMD) and hypovitaminosis D among HIV-infected populations in both RLS and resource rich settings. Although most recognized risk factors for bone loss are similar across settings, in certain RLS there is a high prevalence of both non-HIV-specific risk factors and HIV-specific risk factors, including advanced HIV disease and widespread use of ART, including tenofovir disoproxil fumarate, a non-BMD sparing ART. Of great concern, we neither found published data on the effect of tenofovir disoproxil fumarate initiation on BMD, nor any data on incidence and prevalence of fractures among HIV-infected populations in RLS.To date, the prevalence and squeal of metabolic bone diseases in RLS are poorly described. This review highlights important gaps in our knowledge about HIV-associated bone health comorbidities in RLS. This creates an urgent need for targeted research that can inform HIV care and management guidelines in RLS.http://links.lww.com/COHA/A9. Resource-limited settings (RLS) that constitute low- and middle-income countries  continueet al. involving 884 HIV-infected individuals and 654 controls estimated the prevalence of low BMD among HIV-infected individuals to be as high as 67%, 15% of whom had osteoporosis. The magnitude of low BMD was 6.4 times greater and that of osteoporosis 3.7 times greater than in HIV-uninfected controls [The World Health Organization has categorized low BMD into osteopenia and osteoporosis. In postmenopausal women and men, 50 years and above, osteoporosis is defined as a T-score at or below 2.5 SD whereas osteopenia is defined as a T-score between 1 and 2.5 SD below the young adult mean value. Premenopausal women, men below 50 years or children who have a BMD Z-score at or below 2.0 of the age and sex-matched population are classified as having low bone mass. . In the controls –25. Owincontrols –35. Amoncontrols –39. In acontrols . Among icontrols , regardlcontrols .et al.[In RLS with a disproportionately high burden of HIV and background nutritional deficiencies , known ret al. from Souet al.. Anotheret al. which thet al.. Similaret al.▪,57–60 wet al.–63.There are very limited data in any RLS regarding BMD longitudinal changes among HIV-infected persons. In a 48-week, multisite, second-line trial in South Africa, India, Thailand, Malaysia, and Argentina , HIV-infet al.[A strong body of evidence from longitudinal data in RRS shows that among the different antiretroviral drugs, the potential effect of TDF on bone health is particularly concerning –70. In Aet al. observedet al.. More inet al.. Though et al.–87. TDF et al. and posset al.,80,86–94et al.[P < 0.001).In RLS, the two WHO recommended first line ART treatment regimens for adults and children above 15 years contain TDF; TDF, lamivudine 3TC) and EFV or TDF, emtricitabine (FTC), and EFV, which exposes many HIV-infected individuals to the negative impact of TDF on bone health TC and EF. Converset al. reportedet al.[et al.[et al.[Worldwide, it's estimated that more than one billion people are characterized as having vitamin D deficiency <20 ng/ml), or insufficiency <30 ng/ml) regardless of the economic setting. According to a recent review by Mansueto et al. the prevet al.,97–102 aet al.,103–109 et al. and the et al., Spain [0 ng/ml, et al., and Isret al. to skin  ng/ml reet al.,110–113.et al. which reet al.,114. In et al.. In viewet al.,105. In l.[et al. found thl.[et al.. Though l.[et al. among HIet al.[In RLS, the HIV burden among young adult women is high . Women aet al. showed aWith the scale up of ART, more HIV-infected children are surviving into adolescence. In 2012, an estimated 2.1 million adolescents (10–19 years) were living with HIV in RLS , constitIn 2015, 11 out of the 16 million people receiving ART globally were in the WHO Africa region alone . HoweverCost-effective and feasible strategies to prevent osteoporosis for both HIV-infected and noninfected populations.Identification of simple-low cost tools to detect early osteopenia.Strategies to minimize or avoid ARV-associated bone loss such as ART choice, dose optimization, and ARV switching.Research among HIV-infected populations focusing on women of reproductive age and special populations such as perinatally infected children and adolescents.With more people starting ART  and liviTo successfully conduct research addressing the above mentioned gaps in bone health comorbidities in RLS, there is need to work through several existing research networks either regionally or globally. This will ensure effective design and quality implementation approaches are employed. Importantly, involving key policy makers both domestically and regionally upfront will make the future policy implementation more successful.The review reveals overlapping prevalence of low BMD in RLS and RRS, with a generally higher prevalence of low BMD in RLS overall compared to RRS. We highlight important gaps in our knowledge about HIV-associated bone health comorbidities in RLS. In particular, there are scarce data on bone health mainly from cross-sectional studies that call for urgent need for research that can inform management guidelines in metabolic bone complications in RLS.F.K.M. would like to thank Professors Todd T Brown and Mary Glenn Fowler, Dr Francis Kiweewa, MU-JHU Research Collaboration, Consortium for Advanced Research and Training in Africa, Makerere University School of Public Health and University of the Witwatersrand.F.K.M. has received an R01 grant from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH) under Award Number R01AI118332NIH for bone health-related work as the Principal Investigator, and support as a site investigator on NIH funded microbicide trials network protocols. K.R. has received support from Senior Research Scholar, Thailand Research Fund (TRF) for his work.There are no conflicts of interest.▪ of special interest▪▪ of outstanding interestPapers of particular interest, published within the annual period of review, have been highlighted as:


Hearing loss is considered as the most common sensory disorder in human population that occurs at all ages world-widely and sensorineural hearing loss (SNHL) is the most common type of hearing loss. Various insults could induce SNHL, including acoustic trauma, ear and brain tumors, aging, noise exposure, or ototoxic medications or chemicals. SNHL is caused by irreversible loss of sensory hair cells and/or degeneration of spiral ganglion neurons. SNHL is not yet curable due to the lack of automatic regeneration of hair cells and spiral ganglion neurons in the cochlea. In recent years, exciting animal studies on signaling pathway manipulation, gene therapy, and stem cell transplantation as well as pharmaceutical agents have demonstrated that hair cells and spiral ganglion neurons could be triggered to regenerate, suggesting that hearing loss might be curable eventually in the future. Neural plasticity is the key feature for hair cells and spiral ganglion neurons, and it is especially important for the newly regenerated hair cells and spiral ganglion neurons to be functionally integrated into auditory pathways. In this special issue on neural plasticity of hair cells and spiral ganglion neurons, we are pleased to present a series of articles that represent the latest advances in hair cell development, protection and regeneration, spiral ganglion neuron development and protection, and inherited hearing loss.Hair Cell Development. J. Hang et al.  report that the onset time of hearing may require the expression of prestin and is determined by the functional maturation of outer hair cells. H. Nie et al. (“Plasma Membrane Targeting of Protocadherin 15 Is Regulated by the Golgi-Associated Chaperone Protein PIST”) report that PIST regulates the intracellular trafficking and membrane targeting of the tip-link proteins CDH23 and PCDH15 in hair cells. Hair Cell Damage and Hair Cell Protection. X. Liu et al.  report that enhanced cell-cell adhesion and activation of β-catenin-related canonical Wnt signaling pathway may play a role in the protection of the cochlear from further damage. M. Fu et al. (“The Effects of Urethane on Rat Outer Hair Cells”) report that urethane anesthesia is expected to decrease the responses of outer hair cells, whereas the frequency selectivity of the cochlea remains unchanged. X. Fu et al. (“Loss of Myh14 Increases Susceptibility to Noise-Induced Hearing loss in CBA/CaJ Mice”) report that Myh14 may play a beneficial role in the protection of the cochlea after acoustic overstimulation in CBA/CaJ mice. L. Shi et al. (“Cochlear Synaptopathy and Noise-Induced Hidden Hearing Loss”) provide a brief review to address several critical issues related to NIHHL: mechanisms of noise-induced synaptic damage, reversibility of synaptic damage, functional deficits in NIHHL animal models, evidence of NIHHL in human subjects, and peripheral and central contributions of NIHHL. Hair Cell Regeneration. Y. Shu et al.  report that adenovirus vectors are capable of efficiently and specifically transfecting different cell types in the mammalian cochlea and therefore provide useful tools to study inner ear gene functions and evaluate gene therapies for treating hearing loss and vestibular dysfunction. X. Lu et al.  review recent research progress in hair cell regeneration, synaptic plasticity, and reinnervation of new regenerated hair cells in the mammalian cochlea. C. Wang et al.  report the capability of a behavioral assay in noninvasively evaluating hair cell functions of fish larvae and its potential as a high-throughput screening tool for auditory-related gene and drug discovery. Spiral Ganglion Neuron Development and Protection. P. Chen et al.  report that NLRP3 may have specific functions in spiral ganglion neurons that are altered in both syndromic and nonsyndromic sensorineural deafness. X. Bai et al.  investigated the toxicity of glutamate in spiral ganglion neurons and they found that the protection of edaravone is related to the PI3K pathway and Bcl-2 protein family. Inherited Hearing Loss. X. Gu et al.  identified a missense mutation in the LCCL domain of COCH that is absent in 100 normal hearing controls and cosegregated with impaired hearing. J. Chen et al. (“Identification of a Novel ENU-Induced Mutation in Mouse Tbx1 Linked to Human DiGeorge Syndrome”) confirm the pathogenic basis of Tbx1 in DGS, point out the crucial role of DNA binding activity of Tbx1 for the ear function, and provide additional animal model for studying mechanisms underlying the DGS disease. Y. Guo et al.  report that, for Mandarin Chinese, a tonal language, the temporal E cues of Frequency Region 1 (80–502 Hz) and Region 3  contribute more to the intelligence of sentence recognition than other regions, particularly the region of 80–502 Hz, which contains fundamental frequency (F0) information. L. He et al.  report that mutations in POU4F3 are a relatively common cause (3/16) for ADNSHL in Chinese Hans, which should be routinely screened in such cases during genetic testing. C. Zhang et al.  report the first nonsense mutation of POU4F3 associated with progressive hearing loss and explored the possible underlying mechanism.The articles in this special issue provide valuable insights into development, protection, and regeneration of hair cells and spiral ganglion neurons. By highlighting findings in these articles, we hope this special issue will provide not only new perspectives for future directions in hearing research but also potential therapeutic strategies for treating hearing loss. Renjie Chai  Geng-Lin Li  Jian Wang  Jing Zou


Burkholderia pseudomallei have been previously reported. Therefore the statement “Although melioidosis involves most organs, parotid involvement is rare. To the best of our knowledge, confirmed melioidosis parotitis was not previously reported except for a case that occurred after systemic melioidosis [6]” is inaccurate. It should read :“Pediatric suppurative parotitis caused by B. pseudomallei has already been reported in Thailand by Dance et al. [B. pseudomallei parotitis in Hainan, China.”Since the publication of our article , we havee et al. , who dese et al. , who obs


Plants suffer osmotic and ionic stress under high salinity due to the salts accumulated at the outside of roots and those accumulated at the inside of the plant cells, respectively. Mechanisms of salinity tolerance in plants have been extensively studied and in the recent years these studies focus on the function of key enzymes and plant morphological traits. Here, we provide an updated overview of salt tolerant mechanisms in glycophytes with a particular interest in rice (Oryza sativa) plants. Protective mechanisms that prevent water loss due to the increased osmotic pressure, the development of Na+ toxicity on essential cellular metabolisms, and the movement of ions via the apoplastic pathway (i.e. apoplastic barriers) are described here in detail.Elevated NaThe online version of this article (doi:10.1186/1939-8433-5-11) contains supplementary material, which is available to authorized users. Salini5) (IRRI ). SalineCl . MoreovCl (IRRI ).+ accumulate in excess in plants particularly in leaves over the threshold, which leads to an increase in leaf mortality with chlorosis and necrosis, and a decrease in the activity of essential cellular metabolisms including photosynthesis  and alschroeder ) to plan+ uptake into shoots mediated by the intrusive apoplastic ion transport is considerably high under salinity stress . In rico et al. ; Yadav eo et al. ; Ochiai o et al. ). TherefL p). In case of water uptake in root cells, ΔΨ is the difference between Ψ of extracellular solution and intracellular sap solution. Under non-stress condition, intracellular Ψ is generally more negative than that of the soil solution, resulting in water influx into roots according to the water potential gradient. The water potential (Ψ) is approximately consistent with the sum of the pressure potential (Ψp) and the osmotic potential .Salinity-induced osmotic stress reduces water uptake into plant roots. Plants regulate water transport under salinity stress because a sufficient amount of water is indispensable for the cells to maintain their growth and vital cellular functions such as photosynthesis and metabolisms. In the long distance water transport from roots to shoots, evaporation is one of the main motive forces for the water movement, especially in the apoplastic pathway. Salinity/osmotic stress directly  or indiosm, salinity stress immediately reduces ΔΨ thus water influx. If the water potential gradient is reversed due to severe salinity/osmotic stress , water efflux from roots (dehydration) can occur. To minimize the influence of a reduction in water influx or dehydration upon the growth under salinity/osmotic stress, plants set independent strategies in motion by regulating the root L p (L pr) and attempting to restore ΔΨ . However, time is required  to accumulate enough solutes inside the cell to get a decrease in intracellular Ψosm (osmotic adjustments). Signal transduction and changes of related-gene expression, in contrast, are a relatively quick response . In rica et al. ), but thZea mays) or wheat (Triticum aestivum) was reported to be in a range of 0.5-0.7 MPa  seedlings, no significant change in the L pr has been reported when plants were treated with 100 mM NaCl for 4 hrs in a sharp contrast to the severe L pr repression by 200 mM NaCl treatments for 4 hrs . Such L pr reductions should be effective to prevent dehydration under stress conditions more severe than -0.5 MPa . Severe salinity stress markedly decreases Ψ of the soil solution, which can reverse the osmotic gradient between the inside and the outside of root cell, which generates water efflux (dehydration). In these conditions, shutdown of the water transport attributed to the L pr reduction should be essential to minimize water loss at the initial phase of severe salt stress for survival  Plants shut down L pr even upon moderate salinity stress conditions to get ready for more severe stress in advance because such a sequence occurs in nature ; and (ii) L pr reductions could be a sign of conversion of the growth status of plant cells from the rapid growth mode with high water absorption to the protect/tolerant one with less water uptake as a strategy for the survival under salinity stress . Consis Steudle ; Peyrano Steudle ; Carvaja Steudle ; Martíne Steudle ; Martíne Steudle ; Boursia Steudle ). In rooe et al. ). Howevem et al. ; Hachez m et al. ; Horie em et al. ). Howevee et al. ).L pr was observed in the plants of japonica rice cultivar Nipponbare under salinity stress of 100 mM NaCl within 24 hrs by the pressure chamber method . The result suggests that at least Nipponbare rice plants might not be able to promote an immediate repression of the L pr in response to the osmotic stress phase. Similar exceptions of no influence of salinity stress on L pr have been reported using tobacco  and reln et al. ). Whetheassioura ) and barassioura ) is alsoArabidopsis plants have indicated that PIP aquaporins mediate water uptake by roots and are a predominant component of the L pr  family called aquaporins . Furthel et al. ; Martínel et al. ). These Arabidopsis and maize , which is stimulated by salinity stress . Salinil et al. ), suggese et al. ). The ime et al. ; Boursiae et al. ; Maurel e et al. ; Horie ee et al. ). In Arac et al. ). More rc et al. ). TogethPIPs were identified . Recenti et al. ; Sakuraii et al. ). A ubiqi et al. ). These o et al. ; Li et ao et al. ). These o et al. ). On theo et al. ) and ricosm against an osmotic gradient between root cells and outside saline solution, which eventually restore the water uptake into roots during salinity stress (Greenway and Munns ;;Arabidop and Zhu ). They a and Zhu ). The wou et al. ; Quinteru et al. )  . For moa et al. ). Taken 2+ accumulation identified a candidate locus named HvNax4, which happened to have a considerable influence on the shoot Na+ accumulation  whether the SOS1-type Na+/H+ exchanger exists and plays a primary function in salt tolerant mechanism in barley as in Arabidopsis?, (iii) if so, whether the SOS-like mechanism is a component constituting the high-affinity K+ uptake-coupled Na+ extrusion system in barley roots?, and (iv) whether rice roots exhibit activity of the high-affinity K+ uptake-coupled Na+ extrusion as found in other cereals, in which the OsSOS1-3 protein are involved?A recent genetic study using barley on Znn et al. ). The Hvi et al. ). It hasu et al. ). Furthea et al. ). The rea et al. ). Togeth+ level while keeping the high level of K+, resulting in a high cytosolic K+/Na+ ratio that is preferable for vital cellular metabolisms . It hasn et al. ). The seBlumwald ). Furthe+/H+ antiport activity at the tonoplast membrane was reported in sugar beet . The moe et al. ; Gaxiolae et al. )  indicato et al. ; Rodríguo et al. ; Yamaguco et al. ). Transgo et al. ), suppore et al. ).Arabidopsis, six AtNHX genes were identified, whose gene products can be divided into two classes, class I (AtNHX1-4) and class II (AtNHX5 and 6)  other than SOS3/CBL4. Unlike vacuolar-localized class I transporters, AtNHX5 and 6 class II transporters were postulated to function in endosomal vesicles  and loss of functions of both transporters rendered the atnhx5 atnhx6 double mutant plants more salt sensitive . All clo et al. ). The SOu et al. ). Tonoplu et al. ), suggeso et al. ). A recel et al. ). Moreovl et al. ). These l et al. ). For mol et al. ; Rodrígul et al. ; Yamagucl et al. .+/H+ exchange activity is driven by the vacuolar proton gradient established by two independent proton pumps, vacuolar H+-ATPase (V-ATPase) and vacuolar H+-translocating pyrophosphatase (V-PPase)  . These Plantago maritima plants maintains a greater salt-induced Na+/H+ antiport activity on the tonoplast than that of salt-sensitive Plantago media plants, suggesting that the innate difference in the ability for the Na+ sequestration into vacuoles could be the cause of the difference in salt sensitivity . Theref+ ions that reach the xylem by passing through barrier mechanisms in roots under salinity stress are transported to shoots. In addition to independent barrier components introduced above, plants retain a different protection mechanism at the cell-xylem apoplast interface. It has been shown that Na+ reabsorption occurs from the xylem stream by surrounding tissues, and as a result, reduces the net Na+ flow into shoots .AtHKT1;1 cDNA that encodes a Na+ transporter has been isolated from Arabidopsis plants as a homolog of the TaHKT2;1 gene, which is a Na+/K+ co-transporter in wheat (Triticum aestivum) . The dir et al. ). Severau et al. ; Sunarpiu et al. ; Davenpou et al. ; Horie eu et al. ; Møller u et al. ). Particu et al. ) indicatl Figure . Supportr et al. ). Recente et al. ). Furthei et al. ). Togethi et al. ) . This ms Figure , which ie et al. ; Hauser e et al. ).+ reabsorption mechanisms have been found in cereals such as rice and wheat based on genetic QTL analyses. In rice, the OsHKT1;5 gene has been identified, based on the influence of the shoot K+ content (SKC1) locus on the K+ accumulation in xylem sap and shoots during salinity stress, as one of the primary genes causing a difference in salt tolerance between a tolerant indica cultivar Nona Bokra and a susceptible japonica cultivar . The lon et al. ). Given n et al. ). The Ose et al. ; Hauser e et al. ). In whem et al. ). A mores et al. ; James es et al. ; Byrt ets et al. ). Interes et al. ; James es et al. ). The Nag et al. ), which g et al. ; Hauser g et al. ). Furtheg et al. ; Horie eg et al. ; Hauser g et al. ). Togeth+ loading, the SOS1 transporter in Arabidopsis plants has been suggested to play a crucial role in Na+ retrieval from xylem vessels depending on the degree of salinity stress . This fd Tester ).+ content of barley plants under salinity stress, it has been suggested that salt tolerance is highly associated with the ability to restrict Na+ accumulation in shoots  that mediates K+ loading to the xylem apoplastic space under salinity stress is yet to be determined. However, K+ efflux activity mediated by the K+ outward-rectifying channel (KORC) and/or the nonselective outward-rectifying channel (NORC) (Wegner and Raschke ). + uptake under salinity stress among different rice cultivars have been performed . In facy et al. ). They hy et al. ) have aly et al. ). They hy et al. ; Ranathuy et al. ). A simichreiber ).Arabidopsis root . With ro et al. ) has sheSoil salinity is a serious problem in the world agriculture. Owing to efforts of investigators and elevated levels of technologies, our knowledge on the mechanisms of plant salinity tolerance is dramatically expanding these days. However, individual plant species exhibits distinct salt sensitivity due to morphological differences and the difference in the ability of protection components that the plant has evolved to depend on. Therefore, challenges to elucidate the roles/significances of protection mechanisms in plant salt tolerance including morphological barriers at molecular, cellular and whole plant levels in further depth will be crucial to develop high-yielding salt-tolerant cultivars.


Corrigendum:After publication, we noted terminological issues with the use of rRNA genes and OTUs in the article in addition to typographical issues in the Methods section, Reference list and Acknowledgements. In the “DNA extraction and library preparation” section of the Methods, we have removed “-htp” from the first sentence. In the same paragraph, we have replaced the lowercase u in “ul” with the Greek letter mu. Terminology issues with rDNA genes and rDNA:https://microbiomejournal.biomedcentral.com/submission-guidelines/preparing-your-manuscript/research-articlefor some recommended guidelines about this we were not aware of. We therefore have changed all usage to “16S rRNA genes”. None of these affect the meaning in any way.The terminology we used to describe surveys of 16S rRNA genes was sometimes inappropriate  and also now recommended against, even though it is technically correct (16S rDNA). Some of this was due to simple editing errors (16S rDNA genes) and some of it was using terminology we have previously used but which is now recommended against (16S rDNA). SeeTerminology regarding OTUs vs. species:Additionally, our study made use of common methods to classify sequences into what are known as “OTUs” or operational taxonomic units. We stated that these are used as a proxy for species but did not intend to say “species” in parts of the paper when we meant OTUs. In the Methods and Results and Discussion sections, we wrote that OTUs were a proxy for species for people who were not familiar with OTUs. It was pointed out to us by multiple people that this just confuses the matter and therefore we have therefore removed all uses of “species” when we mean “OTUs”. We have also removed the “proxy” lines. Some of these changes may affect how people interpret our text (if they thought we were truly quantifying species) but do not in any way impact the conclusions of our work. Reference issues:There a number of issues in the references. We have updated the references to add a DOI for Aas et al. (2005); Arndt et al. (2012); Belzer & De Vos (2012); Cogen, Nizet & Gallo (2008); Grice et al. (2009); Knief et al. (2010); Krych et al. (2014); Langille et al. (2014); Linton & Hinton (1988); Liu, Tan & Exley (2015); Murphy et al. (2007); Ribeiro et al. (2011); Schwarzberg et al. (2014); Seifried, Wichels & Gerdts (2015); Steyn et al. (1998); Willems (2014); Young et al. (2007) and Zaura et al. (2009). We have also corrected the titles of Brooks et al. (2015), Maule et al. (2009), McDonald et al. (2011), Novikova et al. (2006) and Venkateswaran et al. (2014). Ichijo et al. (2016) was published with the incorrect issue name (“April”); this has been removed. McMurdie & Susan (2013) has been corrected to McMurdie & Holmes (2013). The author list of Menninger et al. (2013) has been corrected to Dunn et al. (2013); we have also corrected the title. The author list of Caporaso (2012) has been corrected to Caporaso et al. (2012); we have also corrected the title and journal name in addition to adding the volume and pagination information. In-text citations to McMurdie & Susan (2013), Menninger et al. (2013) and Caporaso (2012) have been updated to reflect the correct author list. We have also added a new reference to Wickham (2009) to the reference list and replaced the reference to Wilkinson (2011) on page 7 with this new reference.Acknowledgement Section:There is a spelling error for a name  in the Acknowledgements and the ORCID link / ID is incorrect. We have corrected this to read Steven Kembel and the ORCID ID to be: 0000-0001-5224-0952.


Acute proximal humeral fractures in the elderly are generally treated non-operatively if alignment is acceptable and in stable fracture patterns. When operative treatment is indicated, surgical fixation is often difficult or impossible to obtain. Hemiarthroplasty has long been the standard of care. However, with its reliance on tuberosity healing, functional outcomes and patient satisfaction are often poor. Reverse shoulder arthroplasty has emerged as a new technology for treating proximal humeral fractures but the indications for its use remain uncertain. While not conclusive, the evidence suggests that reverse shoulder arthroplasty yields more consistent results, with improved forward elevation and higher functional outcome scores. The primary advantages of hemiarthroplasty are improved shoulder rotation and shorter operative time. Complication rates do not vary significantly between the two options. Although higher quality trials are needed to further define the role of reverse shoulder arthroplasty, current evidence suggests that this is a reasonable option for surgeons who are highly familiar with its use. Dependi22.1Fractures of the proximal humerus are very common in the elderly population, resulting in approximately 6% of all fractures in adults . While u2.2In 1970, Neer described the classification that is most prevalent today . This cl3High demand and physiologically young patients may have increased tolerance for repeat surgery and it may be reasonable to attempt a reconstruction even in higher grade proximal humerus fractures in this population. Low functional demand patients may be better served with a replacement, and those with pre-morbid symptoms of rotator cuff pathology or evidence of rotator cuff arthrosis may be better served with RSA . RSA is Based on radiographic criteria, primary arthroplasty may be indicated if healing is unlikely or if there is vascular compromise of the humeral head . Fractur4Both HHR and RSA have been extensively described in the literature and the operative techniques are not within the scope of this article . With ra5In one systematic review of patients treated with HHR for proximal humeral fractures, 41% of patients reported unsatisfactory outcomes . However6et al. and Namdari et al. found increased complication rates with RSA as compared to HHR, while Mata-Fink et al. reported better outcomes overall with RSA compared to HHR based on the Constant score, ASES and OSS [No long term outcome studies have been published on RSA in the fracture setting. This has led many authors to question its durability and the wisdom of using this implant in physiologically younger patients for fracture . Current and OSS -11.et al. demonstrated superior forward elevation with RSA with mildly decreased external rotation [et al. similarly found superior forward elevation without a significant decrease in external rotation with RSA [et al. did not observe any significant range of motion differences between the two prostheses [et al. and Namdari et al. [et al. did not find a significant difference in either revision or complication rates [Range of motion (ROM) comparison between the two procedures by Mata-Fink rotation . Ferrellwith RSA . Howeverostheses , and witi et al. , 10. Maton rates . It is iThe results of these three systematic reviews did not demonstrate clear superiority of one prosthetic option over the other. Both appear to be viable options; further prospective studies are needed to further elicit differences in functional outcomes and to further define optimal indications.et al. conducted the only randomized trial in the literature to date comparing RSA with HHR for acute proximal humeral fractures [1. All patients underwent CT scan imaging. There was a minimum 2 year follow-up. A single modular system was used and the post-operative rehabilitation program was standardized across both groups. Functional outcome measures including the Constant, DASH, UCLA scores, active range of motion and tuberosity healing, were significantly higher in patients treated with RSA. The revision rate was lower with RSA. Functional outcomes were poorer with revision of HHR to RSA compared to cases treated with RSA primarily. Successful outcomes in the HHR group were dependent on tuberosity healing. The presence of an irreparable rotator cuff was a strong predictor of failure in HHR [Sebastia-Forcada ractures , Table 1e in HHR .et al. [Baudi et al.  reportedet al. .Cuff and Pupello  comparedet al. [In another retrospective study that compared HHR with RSA, Gallinet et al.  observedet al. .et al. [vs 58 RSA). The Oxford Shoulder Score was higher in the RSA group than the HHR group at 5 years. Revision rates were not significantly different between groups [In 2013, Boyle et al.  reportedn groups .et al. [In a much smaller study, Young et al.  did not et al. [1) treated with HHR or RSA with followup averaging 3.6 years. Patients with RSA had significantly better functional outcomes scores and satisfaction. The RSA patients were older, with a mean age of 80 years compared to 69 years in the HA group; RSA patients had better forward elevation, and higher functional scores as measured by ASES, University of Pennsylvania score and Single Assessment Numeric Evaluation. Quality of life measures and rotation were not significantly different between groups [Garrigues et al. . reporten groups .et al. [In a cost-effectiveness analysis, Chalmers et al.  observedIn summary, both HHR and RSA appear to offer good pain relief with no difference in DASH scores, a measure of disability in daily life, in studies that used this outcome measure. However, functional outcomes in HHR are significantly lower when the tuberosities do not heal, a factor which does not appear to affect the functional outcomes in RSA with the exception of rotation. Survivorship continues to remain a concern with RSA, although revision rates appear to be higher with HHR. The cost of hemiarthroplasty prosthesis is considerably lower than RSA implants; however data suggests that HHR is more expensive when the higher rehabilitation costs are considered. While both HHR and RSA are reasonable implant choices for elderly patients with acute proximal humerus fractures, RSA appears to carry certain advantages, particularly in elderly and low-demand patients, because a successful outcome is much less contingent on tuberosity healing.


Plants, being sessile in nature, are constantly exposed to environmental challenges resulting in substantial yield loss. To cope with harsh environments, plants have developed a wide range of adaptation strategies involving morpho-anatomical, physiological, and biochemical traits. In recent years, there has been phenomenal progress in the understanding of plant responses to environmental cues at the protein level. This progress has been fueled by the advancement in mass spectrometry techniques, complemented with genome-sequence data and modern bioinformatics analysis with improved sample preparation and fractionation strategies. As proteins ultimately regulate cellular functions, it is perhaps of greater importance to understand the changes that occur at the protein-abundance level, rather than the modulation of mRNA expression. This special issue on “Plant Proteomic Research” brings together a selection of insightful papers that address some of these issues related to applications of proteomic techniques in elucidating master regulator proteins and the pathways associated with plant development and stress responses. This issue includes four reviews and 13 original articles primarily on environmental proteomic studies.The first review by Hossain et al.  summarizPanicum virgatum) using the iTRAQ labeling method followed by nano-scale liquid chromatography mass spectrometry analysis. Li et al. [Hylocereus polyrhizus fruits at the posttranscriptional level. Li et al. [Camellia sinensis L.), highlighting the molecular mechanism involved in secondary metabolite production. Zhao et al. [Paeonia lactiflora Pall.) in response to Paclobutrazol, a triazole compound inhibiting growth of lateral branching. By using gel-free proteomics, Alqurashi et al. [Arabidopsis thaliana proteome composition implicating the role of cAMP in biotic and abiotic stress responses by inducing complex changes in cellular energy homeostasis. Rasool et al. [Rhynchophorus ferrugineus Oliv.) using two-dimensional gel electrophoresis (2-DE) and MALDI-TOF mass spectrometry. Liu et al. [Ginkgo biloba L. by exploiting 2-DE coupled with MALDI-TOF/TOF mass spectrometry. Yu et al. [Hosta “Gold Standard” leaves from various regions at different development stages and under excess nitrogen fertilization using 2-DE coupled MALDI-TOF/TOF MS. Findings provide new insights towards understanding the mechanisms of leaf color regulation in variegated leaves. Zhang et al. [Populus deltoids) plants using the 2-DE technique followed by MALDI-TOF-TOF mass spectrometry analysis. Wang et al. [Zea mays), resulting in increased seed protein and lysine contents. The zein, non-zein, and total protein extracts of the seeds of transgenic plants are analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE).Among the 13 original articles, six articles highlight iTRAQ-based proteomic approaches. Ye et al.  present i et al.  provide i et al.  present i et al.  emphasizi et al.  present o et al.  perform i et al.  analyze l et al.  present u et al.  present g et al.  unravel g et al.  demonstrg et al.  provide This special issue on “Plant Proteomic Research” is an attempt to provide researchers with a glimpse of advanced mass spectrometry techniques with a special emphasis on candidate proteins and pathways associated with plant development and stress responses. We believe that this special issue reflects the current perspective and state of the art of plant proteomics, which would not only enrich us in understanding the plant’s response to environmental clues but would further help us in designing better crops with the desired phenotypes. The articles in this issue will be of general interest to proteomic researchers, plant biologists, and environmental scientists.We would like to express our gratitude to all authors for their high quality contributions and numerous peer reviewers for their critical evaluation and valuable suggestions. Moreover, we render our heartiest thanks to the Managing Editor Yong Ren and Section Managing Editor Yue Chen for giving us the opportunity to serve “Plant Proteomic Research” as Guest Editors and Editorial Office, a special mention goes to Sophie Suo for her untiring efforts in coordinating with authors and keeping us updated about the manuscript submission and review process, which helped us in completing the surmount task on time. Finally, we extend our sincere thanks to those professionals whose expertise in proofreading and formatting greatly improved the quality of this special issue.


Sensory pain as assessed with the Pain Perception Scale did not show any significant change. Patients suffering from chronic pain benefited from the multimodal pain treatment up to twelve months after completion of the treatment.Chronic pain has high prevalence rates and is one of the top causes of years lived with disability. The aim of the present study was to evaluate the long-term effects of a multimodal day-clinic treatment for chronic pain. The sample included 183 chronic pain patients  who participated in a four-week multimodal day-clinic treatment for chronic pain. The patients' average current pain intensity (NRS), sensory and affective pain , and depression and anxiety (HADS) were assessed at pre- and posttreatment, as well as at three follow-ups . Multilevel models for discontinuous change were performed to evaluate the change of the outcome variables. Improvements from pretreatment to posttreatment and from pretreatment to all follow-ups emerged for pain intensity (NRS; 0.54 ≤  Chronic pain is a major health care problem. A recent review and meta-analysis including 86 studies found an average prevalence estimate of 31% , as wellefficacy in RCTs under controlled conditions and their effectiveness under clinically representative conditions  and Pöhlmann et al. [25] (both  d=0.7). Compared with Schütze et al. [d=0.10–0.20) and Ruscheweyh et al. [d=0.26), the improvement at posttreatment regarding symptoms of anxiety represents a slightly higher effect (d=0.40). Compared to Borys et al. [d=0.55), however, the effect on anxiety at discharge was lower. At 12-month follow-up, anxiety improved (d=0.34) slightly more than that in Borys et al. [d=0.22). Anxiety at 12-month follow-up was not different from baseline in the study by Ruscheweyh et al. [The reduction of depressive symptoms at the end of the treatment s et al.  (d=0.77)i et al.  (d=0.7),n et al.  (d=0.80)s et al. , Hampel s et al. , and Russ et al.  who repoe et al.  s et al.  (d=0.55)s et al.  (d=0.22)s et al. h et al. . Corresph et al. , depressThe data of the current study were collected in a naturalistic setting. This enhances the external validity of the results. But as the study was neither randomized nor controlled, the internal validity of the results is limited. Therefore, we cannot exclude confounders like time effects as possible causes for the found improvements. Yet, a 4-year follow-up study on the course of chronic pain in the community reported that chronic pain shows low recovery rates . NeverthAs chronic pain is most probably caused by an interaction of biopsychosocial factors, multimodal pain treatment programs seem to provide the most effective therapy. The current study supports the notion that chronic pain patients benefit from multimodal treatments under the conditions of routine care in the long term.