Diabetic foot ulcers segmentation challenge report: Benchmark and analysis.

Monitoring the healing progress of diabetic foot ulcers is a challenging process. Accurate segmentation of foot ulcers can help podiatrists to quantitatively measure the size of wound regions to assist prediction of healing status. The main challenge in this field is the lack of publicly available manual delineation, which can be time consuming and laborious. Recently, methods based on deep learning have shown excellent results in automatic segmentation of medical images, however, they require large-scale datasets for training, and there is limited consensus on which methods perform the best. The 2022 Diabetic Foot Ulcers segmentation challenge was held in conjunction with the 2022 International Conference on Medical Image Computing and Computer Assisted Intervention, which sought to address these issues and stimulate progress in this research domain. A training set of 2000 images exhibiting diabetic foot ulcers was released with corresponding segmentation ground truth masks. Of the 72 (approved) requests from 47 countries, 26 teams used this data to develop fully automated systems to predict the true segmentation masks on a test set of 2000 images, with the corresponding ground truth segmentation masks kept private. Predictions from participating teams were scored and ranked according to their average Dice similarity coefficient of the ground truth masks and prediction masks. The winning team achieved a Dice of 0.7287 for diabetic foot ulcer segmentation. This challenge has now entered a live leaderboard stage where it serves as a challenging benchmark for diabetic foot ulcer segmentation.

An operational maintenance approach for improving physiological monitor by HFMEA process: an empirical case study.

This study explored the application of healthcare failure mode and effect analysis (HFMEA) to identify and evaluate risk-associated factors in the intensive care unit (ICU) through a clinical-based expert knowledge (decision) for the physiological monitor operational maintenance process. Methods and intervention: A mixed qualitative and quantitative proactive approach to explore the HFMEA process by analyzing 20 units of physiological monitors in the ICU. An HFMEA expert team of six people was formed to perform a risk-based analysis and evaluate the potential hazard index, mitigating the hazard scores and risks. Results: From the main processes and possible failure reasons, one high-risk hazard index greater than or equal to 8 of the standard score was found. This standard score indicates the signed manufacturer's contract for maintenance was the hazard index failure mode on the parts not regularly replaced according to the contract. This systematic hazard index failure mode shows the highest hazard scores in the possible failure reason category, established as a standard maintenance procedure. In addition, the HFMEA expert analysis of the 20 units of physiological monitors within 6 months of the original and remanufactured part maintenance results in operational availability from 90.9% for self-repair to 99.2% for contract manufacturer repair. Conclusions: This study concludes a systematic reference in malpractices caused by maintenance negligence. The HFMEA expert team agrees that hazard failure scores greater than or equal to 8 are vital assessments and evaluations for decision-making, especially in maintaining healthcare intensive unit care physiological monitors.

Comparing the associations of three psychometric scales at baseline with long-term prognosis of depression over a 10-year period.

OBJECTIVE: The Depression and Somatic Symptoms Scale (DSSS), a free scale, includes depression (DS) and somatic (SS) subscales. This study aimed to compare the associations of the baseline DSSS, Hamilton Depression Rating Scale (HAMD) and Hospital Anxiety and Depression Scale (HADS) scores with the outcome of depression over a 10-year follow-up period. METHODS: Two hundred ninety outpatients with major depressive disorder (MDD) were enrolled and were followed-up at the 6-month, 2-year, and 10-year points. The three scales were administered at each follow-up. Multiple linear regressions were used to compare the associations. RESULTS: In a comparison of the HAMD, DS, and HADS-depression, the HAMD and DS scores at baseline were most strongly associated with the HAMD score at two (6-month and 2-year) and one (10-year) follow-up points, respectively. In a comparison of the HAMD, DS, SS, HADS-depression, and HADS-anxiety, the SS and HAMD scores at baseline were most strongly associated with the HAMD score at two (6-month and 10-year) and one (2-year) follow-up points, respectively. CONCLUSIONS: The DS, SS, and HAMD scores at baseline were significantly associated with the long-term outcome of depression. Scales or subscales assessing somatic symptoms might be more strongly associated with the outcome of depression.

The SRSF3-MBNL1-Acin1 circuit constitutes an emerging axis to lessen DNA fragmentation in colorectal cancer via an alternative splicing mechanism.

Altered alternative splicing (AS) events are considered pervasive causes that result in the development of carcinogenesis. Herein, we identified reprogrammed expression and splicing profiles of Muscle blind-like protein 1 (MBNL1) transcripts in tumorous tissues compared to those of adjacent normal tissues dissected from individual colorectal cancer (CRC) patients using whole-transcriptome analyses. MBNL1 transcript 8 (MBNL18) containing exons 5 and 7 was majorly generated by cancerous tissues and CRC-derived cell lines compared with those of the normal counterparts. Interplay between the exonic CA-rich element and upregulated SRSF3 facilitated the inclusion of MBNL1 exons 5 and 7, which encode a bipartite nuclear localization signal (NLS) and conformational NLS. Moreover, abundant SRSF3 interfered with the autoregulatory mechanism involved in utilization of MBNL1 exons 5 and 7, resulting in enrichment of the MBNL18 isoform in cultured CRC cell lines. Subsequently, an increase in the MBNL18 isoform drove a shift in the apoptotic chromatin condensation inducer in nucleus 1-S (Acin1-S) isoform to the Acin1-L isoform, leading to diminished DNA fragmentation in cultured CRC cells under oxidative stress. Taken together, SRSF3-MBNL1-Acin1 was demonstrated to constitute an emerging axis which is relevant to proapoptotic signatures and post-transcriptional events of CRC cells.

Comorbidity with more anxiety disorders associated with a poorer prognosis persisting at the 10-year follow-up among patients with major depressive disorder.

OBJECTIVE: No study has investigated the association between number of anxiety disorders (NADs) and long-term outcome over 10 years among patients with major depressive disorder (MDD). This study investigated this issue. METHODS: At baseline, 290 outpatients with MDD were enrolled, 149 with at least one anxiety disorder (AD). Subjects were followed-up at six-month, two-year, and 10-year points. The Structured Clinical Interview for DSM-IV-TR was used to confirm psychiatric diagnoses. NADs at baseline was recorded. The Hamilton Depression Rating Scale (HAMD), the anxiety subscale of the Hospital Anxiety and Depression Scale (HADS-A), and the somatic subscale (SS) of the Depression and Somatic Symptoms Scale were employed. Generalized Estimating Equation models were used for statistical analysis. RESULTS: MDD patients with ADs had greater depression, anxiety, and somatic severities at the three follow-up points than those without. NADs was significantly and positively correlated with the three dimensions and total duration of pharmacotherapy at follow-up. NADs was independently associated with symptom severity after controlling for depression and anxiety at baseline and pharmacotherapy. When the DSM-5 criteria for ADs were applied, the results were unchanged. Specific phobia, panic disorder and social phobia, and panic disorder and specific phobia were independently associated with depression, anxiety, and somatic symptoms, respectively. LIMITATION: Pharmacotherapy at follow-up was not controlled. The three follow-up intervals were unequal. CONCLUSIONS: Comorbidity with more ADs was associated with a poorer prognosis. The negative impacts of ADs on MDD persisted at the ten-year follow-up point. NADs was associated with the long-term prognosis of MDD.

Structural and Functional Determinants of Rodent and Human Surfactant Protein A: A Synthesis of Binding and Computational Data.

Surfactant protein A (SP-A) provides surfactant stability, first line host defense, and lung homeostasis by binding surfactant phospholipids, pathogens, alveolar macrophages (AMs), and epithelial cells. Non-primates express one SP-A protein whereas humans express two: SP-A1 and SP-A2 with core intra- and inter-species differences in the collagen-like domain. Here, we used macrophages and solid phase binding assays to discern structural correlates of rat (r) and human (h) SP-A function. Binding assays using recombinant rSP-A expressed in insect cells showed that lack of proline hydroxylation, truncations of amino-terminal oligomerization domains, and site-directed serine (S) or alanine (A) mutagenesis of cysteine 6 (C6S), glutamate 195 (E195A), and glutamate 171 (E171A) in the carbohydrate recognition domain (CRD) all impaired SP-A binding. Replacement of arginine 197 with alanine found in hSP-A (R197A), however, restored the binding of hydroxyproline-deficient rSP-A to the SP-A receptor SP-R210 similar to native rat and human SP-A. In silico calculation of Ca++ coordination bond length and solvent accessibility surface area revealed that the "humanized" R197A substitution alters topology and solvent accessibility of the Ca++ coordination residues of the CRD domain. Binding assays in mouse AMs that were exposed to either endogenous SP-A or hSP-A1 (6A2) and hSP-A2 (1A0) isoforms in vivo revealed that mouse SP-A is a functional hybrid of hSP-A1 and hSP-A2 in regulating SP-A receptor occupancy and binding affinity. Binding assays using neonatal and adult human AMs indicates that the interaction of SP-A1 and SP-A2 with AMs is developmentally regulated. Furthermore, our data indicate that the auxiliary ion coordination loop encompassing the conserved E171 residue may comprise a conserved site of interaction with macrophages, and SP-R210 specifically, that merits further investigation to discern conserved and divergent SP-A functions between species. In summary, our findings support the notion that complex structural adaptation of SP-A regulate conserved and species specific AM functions in vertebrates.

Migraine with active headache was associated with other painful physical symptoms at two-year follow-up among patients with major depressive disorder.

BACKGROUND: Few studies have investigated the associations of comorbid migraine with other painful physical symptoms (PPS) in patients with major depressive disorder (MDD) at the two-year follow-up point. This study aimed to investigate this issue. METHODS: At baseline, 155 outpatients with MDD were enrolled. Migraine was diagnosed at baseline according to the International Classification of Headache Disorders. At follow-up, data of 101 subjects were analyzed. The average intensities of head, bone and/or joints, back, chest, abdomen, neck and/or shoulder, general muscle, and limb pain in the past week were evaluated using a visual analog scale (VAS). At follow-up, active headache was defined as a score on the VAS > 3. Multiple linear regressions were used to investigate the associations of migraine at baseline with other PPS at follow-up. RESULTS: Compared with the migraine with inactive headache group and the non-migraine group, patients with migraine with active headache had significantly higher intensities of other PPS and a lower remission rate of depression. There were no significant differences in the pain intensities of the other seven PPS between the migraine with inactive headache group and the non-migraine group. Headache intensity was significantly correlated with the intensities of other PPS at baseline and follow-up. Migraine with active headache independently predicted other PPS after controlling for depression and anxiety at baseline. CONCLUSIONS: Migraine with active headache among MDD patients could predict other PPS. Prevention and treatment of headache might help to decrease other PPS and improve the prognosis of depression. Integration of treatment for depression and headache is indicated.

Persistent depressive disorder has long-term negative impacts on depression, anxiety, and somatic symptoms at 10-year follow-up among patients with major depressive disorder.

OBJECTIVE: The study aimed to investigate the impacts of persistent depressive disorder (PDD) and pharmacotherapy on depression, anxiety, and somatic symptoms among patients with major depressive disorder (MDD) over a ten-year period. METHODS: 290 outpatients with MDD were enrolled, including 117 with PDD, at baseline. Subjects were followed-up at six-month, two-year, and 10-year points. MDD and dysthymic disorder were diagnosed using the Structured Clinical Interview for DSM-IV-TR. The Hamilton Depression Rating Scale, the Hospital Anxiety and Depression Scale, and the Depression and Somatic Symptoms Scale were used. Generalized Estimating Equation models were used to investigate the impacts. RESULTS: MDD patients with PDD had greater severities of depression, anxiety, and somatic symptoms at the three follow-up points as compared with those without; however, these results were of statistical significance only in patients without pharmacotherapy. MDD patients with PDD had a longer duration of pharmacotherapy and a lower remission rate as compared with those without. After controlling for depression and anxiety at baseline, PDD was independently associated with more severe depression, anxiety, and somatic symptoms. LIMITATION: At the ten-year follow-up, approximately half of the subjects were lost to follow-up; this, in addition to the unequal follow-up intervals, might have caused bias. CONCLUSIONS: Among the patients, PDD continued to have negative impacts on depression, anxiety, and somatic symptoms over the subsequent ten years. Differences in symptomatology between the patients with and without PDD were statistically insignificant when pharmacotherapy was utilized; however, pharmacotherapy did not fully compensate for the negative impacts of PDD.

Migraine and greater pain symptoms at 10-year follow-up among patients with major depressive disorder.

BACKGROUND: No study has investigated the associations of migraine with pain symptoms over a ten-year period among outpatients with major depressive disorder (MDD). This study aimed to investigate this issue. METHODS: At baseline, the study enrolled 290 outpatients with MDD and followed-up the patients at six-month, two-year, and ten-year time points. MDD and anxiety comorbidities were diagnosed using the Structured Clinical Interview for DSM-IV-text revision. Migraine was diagnosed based on the International Classification of Headache Disorders. The bodily pain subscale of the Short Form 36 (SF-BP) and the pain subscale (PS) of the Depression and Somatic Symptoms scale were also used. Generalized Estimating Equation models were employed to investigate the longitudinal impacts of migraine on pain symptoms. RESULTS: MDD patients with migraine had lower SF-BP and higher PS scores than those without. Depression, anxiety, and headache indices were significantly correlated with SF-BP and PS scores. The higher the frequency of migraine, the more often patients suffered from pain symptoms. Patients with migraine at all investigated time points suffered from pain symptoms most of the time (ranging from 60.0% to 73.7%) over the 10 years. After controlling for depression and anxiety, migraine was independently associated with a decreased SF-BP score (by 8.93 points) and an increased PS score (by 1.33 points). CONCLUSION: Migraine was an important comorbidity associated with greater severities of pain symptoms during long-term follow-up. Migraine treatment should be integrated into the treatment of depression to improve pain symptoms and quality of life in the pain dimension.

Untreated duration predicted the severity of depression at the two-year follow-up point.

BACKGROUND: No study has investigated the impact of the duration of untreated depression (DUD) on the severity of depression at the two-year follow-up point in patients with major depressive disorder (MDD) who discontinued pharmacotherapy. This study aimed to investigate this issue. METHODS: This study enrolled 155 subjects with MDD at baseline, and 101 subjects who had discontinued pharmacotherapy for 17.1 ± 5.8 months were assessed at the two-year follow-up point. DUD was defined as the interval between the onset of the index major depressive episode and the start of pharmacotherapy. The 17-item Hamilton Depression Rating Scale (HAMD) was used to evaluate depression. Multiple linear regressions were used to examine the impacts of DUD on the severity and improvement percentage (IP) of depression at follow-up. RESULTS: A longer DUD was significantly associated with a greater severity and a lower IP of depression at follow-up. After controlling for confounding factors, DUD was the most significant factor predicting the severity and IP of depression at follow-up. DUD was more strongly associated with the prognosis of depression at follow-up than depression and anxiety severities at baseline. CONCLUSIONS: The DUD at baseline independently predicted the severity of depression at the two-year follow-up point. Although the patients had discontinued pharmacotherapy for nearly 1.5 years, the impact of the DUD on the severity of depression persisted at follow-up. The DUD was an important index that predicted the severity of depression at the two-year follow-up point.

Unintentional Injuries among Psychiatric Outpatients with Major Depressive Disorder.

BACKGROUND: No study has investigated the percentages of and factors related to unintentional injuries among psychiatric outpatients with major depressive disorder (MDD). This study aimed to investigate these issues. METHODS: One-hundred and forty-one outpatients with MDD at baseline were enrolled from psychiatric outpatients by systematic sampling, and 119 subjects attended a one-year follow-up. Self-reported unintentional injuries in the past one year were recorded. Psychiatric disorders were diagnosed using the Structured Clinical Interview for DSM-IV-TR. The severity of depression was evaluated by the Hamilton Depression Rating Scale. Other data, including body weight and height, cigarette smoking, headaches, and medications, were collected. Generalized Estimating Equations were used to investigate independent factors related to unintentional injuries. RESULTS: At baseline and follow-up, 40.4% and 27.7% of subjects had experienced at least one unintentional injury in the past one year, respectively. About half of subjects with unintentional injuries needed medical treatment for injuries and had functional impairment due to injuries. A greater severity of depression, cigarette smoking, a higher body mass index, and an older age were independent risk factors related to unintentional injuries. CONCLUSION: Unintentional injuries that increased the medical burden and functional impairment were common among outpatients with MDD and should not be neglected. Treatment of depression, control of body weight, and quitting cigarettes might be helpful to prevent unintentional injuries.

Headache: an important factor associated with muscle soreness/pain at the two-year follow-up point among patients with major depressive disorder.

BACKGROUND: No study has compared the associations of headache, anxiety, and depression at baseline with muscle soreness or pain (MS/P) at baseline and at the two-year follow-up point among outpatients with major depressive disorder (MDD). This study aimed to investigate the above issue. METHODS: This study enrolled 155 outpatients with MDD at baseline, and 131 attended a two-year follow-up appointment. At baseline, migraine was diagnosed based on the International Classification of Headache Disorders, 2(nd) edition. MDD and anxiety disorders were diagnosed using the Structured Clinical Interview for DSM-IV-TR. The visual analog scale was used to evaluate the intensities of headache and MS/P in the neck, shoulder, back, upper limbs, and lower limbs. Depression and anxiety were evaluated using the Hospital Anxiety and Depression Scale. Multiple linear regressions were used to compare the associations of these factors with MS/P. RESULTS: Compared with anxiety disorders, migraine was more strongly associated with MS/P in all areas at baseline and in the upper and lower limbs at follow-up. Headache intensity at baseline was the factor most strongly associated with MS/P in all areas at baseline and follow-up after controlling for depression and anxiety. Headache intensity at baseline predicted MS/P at baseline and follow-up. CONCLUSIONS: Migraine and headache intensity are important factors related to MS/P at baseline and follow-up among patients with MDD. Integrating depression and headache treatment might be indicated to improve MS/P.

The impact of the duration of an untreated episode on improvement of depression and somatic symptoms.

PURPOSE: The aim of this study was to investigate the impact of the duration of an untreated episode (DUE) on the improvement of depression and somatic symptoms among patients with major depressive disorder (MDD), after the patients had received 4 weeks of pharmacotherapy. METHODS: In this open-label study, there were 155 participants with MDD who were treated daily with 75 mg of venlafaxine for 4 weeks. DUE was defined as the interval between the onset of the index major depressive episode and the start of pharmacotherapy. The Depression and Somatic Symptoms Scale (DSSS), composed of the depression subscale (DS) and the somatic subscale (SS), was used. The SS included the pain subscale (PS) and the nonpain somatic subscale (NPSS). Multiple linear regressions were used to test the impacts of DUE on the improvement percentages (IPs) of depression and somatic symptoms. RESULTS: Eighty-five subjects completed the 4-week treatment. The IPs of the DS, SS, and NPSS were significantly negatively correlated with DUE. A shorter DUE was related to higher IPs. DUE was an independent factor, predicting the IPs of the DS, SS, and NPSS. DUE <1 month was the most powerful time-point to predict the IPs of the DS, SS, and NPSS. However, DUE was unable to predict the IP of the PS at all time-points. CONCLUSION: A shorter DUE might be one of the factors related to greater improvement of depression and somatic symptoms. DUE should be considered as an important factor when investigating the prognosis of depression and somatic symptoms.

Centrin 3 is an inhibitor of centrosomal Mps1 and antagonizes centrin 2 function.

Centrins are a family of small, calcium-binding proteins with diverse cellular functions that play an important role in centrosome biology. We previously identified centrin 2 and centrin 3 (Cetn2 and Cetn3) as substrates of the protein kinase Mps1. However, although Mps1 phosphorylation sites control the function of Cetn2 in centriole assembly and promote centriole overproduction, Cetn2 and Cetn3 are not functionally interchangeable, and we show here that Cetn3 is both a biochemical inhibitor of Mps1 catalytic activity and a biological inhibitor of centrosome duplication. In vitro, Cetn3 inhibits Mps1 autophosphorylation at Thr-676, a known site of T-loop autoactivation, and interferes with Mps1-dependent phosphorylation of Cetn2. The cellular overexpression of Cetn3 attenuates the incorporation of Cetn2 into centrioles and centrosome reduplication, whereas depletion of Cetn3 generates extra centrioles. Finally, overexpression of Cetn3 reduces Mps1 Thr-676 phosphorylation at centrosomes, and mimicking Mps1-dependent phosphorylation of Cetn2 bypasses the inhibitory effect of Cetn3, suggesting that the biological effects of Cetn3 are due to the inhibition of Mps1 function at centrosomes.

The Impacts of Migraine among Outpatients with Major Depressive Disorder at a Two-Year Follow-Up.

BACKGROUND: No study has investigated the impacts of migraine on depression, anxiety, and somatic symptoms and remission at the two-year follow-up point among patients with major depressive disorder (MDD). This study aimed to investigate the above issues. METHODS: Psychiatric outpatients with MDD recruited at baseline were investigated at a two-year follow-up (N = 106). The Hamilton Depression Rating Scale, Hospital Anxiety and Depression Scale, and Depression and Somatic Symptoms Scale were used. Migraine was diagnosed according to the International Classification of Headache Disorders, 2nd edition. The patients were divided into no migraine, inactive migraine, and active migraine subgroups. Multiple logistic regressions were used to investigate the significant factors related to full remission of depression. RESULTS: Among patients without pharmacotherapy at the follow-up, patients with active migraine had significantly greater severities of anxiety and somatic symptoms as compared with patients without migraine; moreover, patients with active migraine had the lowest improvement percentage and full remission rate. There were no significant differences in depression, anxiety, and somatic symptoms between patients with inactive migraine and those without migraine. Active headache at follow-up was a significant factor related to a lower full remission rate. CONCLUSIONS: Active headache at follow-up was associated with a lower rate of full remission and more residual anxiety and somatic symptoms at follow-up among patients with migraine. Physicians should integrate a treatment plan for depression and migraine for the treatment of patients with MDD.

The impacts of migraine and anxiety disorders on painful physical symptoms among patients with major depressive disorder.

BACKGROUND: No study has simultaneously investigated the impacts of migraine and anxiety disorders on painful physical symptoms (PPS) among patients with major depressive disorder (MDD). The study aimed to investigate this issue. METHODS: This open-label study enrolled 155 outpatients with MDD, who were then treated with venlafaxine 75 mg per day for four weeks. Eighty-five participants with good compliance completed the treatment. Migraine was diagnosed according to the International Classification of Headache Disorders. MDD and anxiety disorders were diagnosed using the Structured Clinical Interview for DSM-IV-TR. The visual analog scale (VAS) was used to evaluate the severity of eight PPS. Multiple linear and logistic regressions were used to investigate the impacts of migraine and anxiety disorders on PPS. RESULTS: Compared with patients without migraine, patients with migraine had a greater severity of PPS at baseline and post-treatment. After controlling for demographic variables and depressive severity, migraine independently predicted the intensities of eight PPS at baseline and four PPS post-treatment. Moreover, migraine independently predicted poorer treatment responses of chest pain and full remission of pains in the head, chest, neck and/or shoulder. Anxiety disorders predicted less full remission of pains in the abdomen and limbs. CONCLUSION: Migraine and anxiety disorders have negative impacts on PPS among patients with MDD. Integrating the treatment of migraine and anxiety disorders into the management of depression might help to improve PPS and the prognosis of MDD.

Residual symptoms related to physical and panic symptoms at baseline predict remission of depression at follow-up.

AIMS: The study aimed to investigate whether common residual symptoms at baseline were able to predict full remission of depression at 6-month and 2-year follow-up examinations in patients with major depressive disorder (MDD). METHODS: This study enrolled 135 outpatients with MDD. The depression (DS) and somatic subscales (SS) of the Depression and Somatic Symptoms Scale and the depression and anxiety (HADS-A) subscales of the Hospital Anxiety and Depression Scale were used to investigate residual symptoms, which were divided into the common residual part (CRP) and the other residual part (ORP). Multivariate logistic regression was used to compare the ability to predict full remission between the CRP and ORP scores at baseline. RESULTS: One hundred and nineteen and 106 outpatients completed the two follow-up examinations. The CRP of the DS and the ORP of the SS and HADS-A at baseline had a good ability to predict full remission among patients without pharmacotherapy. The three residual parts included physical and anxiety symptoms of depression and panic symptoms. CONCLUSIONS: Physicians should pay attention to physical, anxiety, and panic symptoms, because these symptoms are related to remission of depression. Future studies should explore how these symptoms affect the prognosis of depression.

Multiple resistance-activating substances produced by Humicola phialophoroides isolated from soil for control of Phytophthora blight of pepper.

BACKGROUND: Microorganisms capable of utilizing vegetable tissues for multiplication in soil were isolated, cultivated in liquid medium prepared from the same vegetable tissues, and tested for ability to activate resistance in pepper leaves against Phytophthora blight caused by Phytophthora capsici. RESULTS: Among the 121 microorganisms isolated, a fungus Humicola phialophoroides showed distinct ability to produce substances capable of activating resistance. The resistance-activating substances produced by H. phialophoroides were mostly retained in the mycelium, and were readily extracted from the mycelium powder with polar solvents. The extract was not inhibitory to zoospore germination or germ tube growth of P. capsici. In pepper leaves, the extract took only about 12 h to activate resistance against P. capsici. After activation, washing treated leaf surface with water did not have much effect on the resistance expression. In addition to being able to move from the upper leaf surface to lower leaf surface, the resistance-activating substances were capable of moving 5 mm acropetally and 10 mm basipetally in pepper leaves, Chromatography of the extract on silica gel column suggests that there are probably more than three components in the extract with resistance-activating ability. The resistance-activating activity of the mycelium extract was not affected by treatment with either cation or anion exchange resins, indicating that none of the active components have positive or negative charges on their molecules. CONCLUSION: Results show that H. phialophoroides is capable of producing multiple resistance-activating substances which are mostly retained in the mycelium. The study also indicates that none of the active components have positive or negative charges on their molecules.

MPS1/Mph1 phosphorylates the kinetochore protein KNL1/Spc7 to recruit SAC components.

The genomic stability of all organisms depends on the precise partition of chromosomes to daughter cells. The spindle assembly checkpoint (SAC) senses unattached kinetochores and prevents premature entry to anaphase, thus ensuring that all chromosomes attach to opposite spindle poles (bi-orientation) during mitosis. MPS1 is an evolutionarily conserved protein kinase required for the SAC and chromosome bi-orientation. Yet, its primary cellular substrate has remained elusive. We show that fission yeast Mph1 (MPS1 homologue) phosphorylates the kinetochore protein Spc7 (KNL1/Blinkin homologue) at the MELT repeat sequences. This phosphorylation promotes the in vitro binding to the Bub1-Bub3 complex, which is required for kinetochore-based SAC activation (Mad1-Mad2-Mad3 localization) and chromosome alignment. Accordingly, a non-phosphorylatable spc7-12A mutation abolishes kinetochore targeting of Bub1-Bub3, whereas a phospho-mimetic spc7-12E mutation forces them to localize at kinetochores throughout the entire cell cycle, even in the absence of Mph1. Thus, MPS1/Mph1 kinase locating at the unattached kinetochores initially creates a mark, which is crucial for SAC activation and chromosome bi-orientation. This mechanism seems to be conserved in human cells.

Negative impact of migraine on quality of life after 4 weeks of treatment in patients with major depressive disorder.

AIM: The impact of migraine on health-related quality of life (HRQoL) among patients with major depressive disorder (MDD) after acute antidepressant treatment has not been addressed. The aim of the present study was to investigate whether or not the negative impact of migraine on HRQoL among outpatients with MDD continued to have an effect after 4 weeks of venlafaxine treatment. METHODS: A total of 135 outpatients with MDD were enrolled, who were then treated with venlafaxine 75 mg per day for 4 weeks in the present open-label study. Migraine was diagnosed based on the International Classification of Headache Disorders (2nd edn). Changes in Short-Form 36 (SF-36) and Hamilton Depression Rating Scale (HAMD) scores were the outcome measures. Multiple linear regression was used to assess whether migraine was an independent factor predicting SF-36 score after treatment. RESULTS: Seventy-two participants (18M/54F) completed the 4-week treatment. Subjects with migraine had a poorer HRQoL in terms of bodily pain and mental health at baseline. Subjects with and without migraine showed significant improvement in all SF-36 subscales and depression after treatment, but subjects with migraine still had a poorer HRQoL regarding bodily pain and physical functioning after treatment as compared with those without migraine. Migraine could predict a negative outcome after treatment in the subscales of physical functioning, role limitations-physical, and role limitations-emotional. CONCLUSIONS: Migraine may have a negative impact on the improvement of partial SF-36 subscales, especially on functional recovery, after acute treatment among outpatients with MDD. Whether additional intervention besides antidepressant treatment for migraine is indicated may need further study.