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.

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.

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.

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.

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.

Surfactant protein A (SP-A)-mediated clearance of Staphylococcus aureus involves binding of SP-A to the staphylococcal adhesin eap and the macrophage receptors SP-A receptor 210 and scavenger receptor class A.

Staphylococcus aureus causes life-threatening pneumonia in hospitals and deadly superinfection during viral influenza. The current study investigated the role of surfactant protein A (SP-A) in opsonization and clearance of S. aureus. Previous studies showed that SP-A mediates phagocytosis via the SP-A receptor 210 (SP-R210). Here, we show that SP-R210 mediates binding and control of SP-A-opsonized S. aureus by macrophages. We determined that SP-A binds S. aureus through the extracellular adhesin Eap. Consequently, SP-A enhanced macrophage uptake of Eap-expressing (Eap(+)) but not Eap-deficient (Eap(-)) S. aureus. In a reciprocal fashion, SP-A failed to enhance uptake of Eap(+) S. aureus in peritoneal Raw264.7 macrophages with a dominant negative mutation (SP-R210(DN)) blocking surface expression of SP-R210. Accordingly, WT mice cleared infection with Eap(+) but succumbed to sublethal infection with Eap- S. aureus. However, SP-R210(DN) cells compensated by increasing non-opsonic phagocytosis of Eap(+) S. aureus via the scavenger receptor scavenger receptor class A (SR-A), while non-opsonic uptake of Eap(-) S. aureus was impaired. Macrophages express two isoforms: SP-R210(L) and SP-R210(S). The results show that WT alveolar macrophages are distinguished by expression of SP-R210(L), whereas SR-A(-/-) alveolar macrophages are deficient in SP-R210(L) expressing only SP-R210(S). Accordingly, SR-A(-/-) mice were highly susceptible to both Eap(+) and Eap(-) S. aureus. The lungs of susceptible mice generated abnormal inflammatory responses that were associated with impaired killing and persistence of S. aureus infection in the lung. In conclusion, alveolar macrophage SP-R210(L) mediates recognition and killing of SP-A-opsonized S. aureus in vivo, coordinating inflammatory responses and resolution of S. aureus pneumonia through interaction with SR-A.

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.

The cut-off points of the Depression and Somatic Symptoms Scale and the Hospital Anxiety and Depression Scale in detecting non-full remission and a current major depressive episode.

OBJECTIVE: This study aimed to ascertain the cut-off scores of the Depression and Somatic Symptoms Scale (DSSS) for non-full remission (FR) and a current major depressive episode (MDE) and compare the discriminative abilities of the DSSS and the Hospital Anxiety and Depression Scale (HADS). METHODS: One-hundred and nineteen depressive outpatients who completed a 6-month follow-up were used to ascertain the cut-off scores for non-FR, defined as a Hamilton Depression Rating Scale score ≥ 8; another 214 consecutive outpatients were assessed to identify the cut-off scores for a MDE, as defined by the Structured Clinical Interview for DSM-IV-TR. Receiver operating characteristic (ROC) analysis was used to ascertain the cut-off scores. RESULTS: The area under the ROC curve was greatest for the DSSS depression subscale (DS), followed by the HADS depression subscale (HADS-D). The cut-off scores for non-FR were a DS score ≥ 9 (sensitivity and specificity: 88.7 and 71.9%, respectively) and a HADS-D score ≥ 8 (77.4 and 84.2%), and the cut-off scores for a MDE were a DS score ≥ 19 (86.3 and 75.6%) and a HADS-D score ≥ 11 (77.9 and 76.5%). CONCLUSIONS: The DSSS and HADS can be used to distinguish different depressive states. The results demonstrated the discriminative validity of the DSSS and the HADS.

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.

Comparative metabolism of 1,2,3,3,3-pentafluoropropene in male and female mouse, rat, dog, and human liver microsomes and cytosol and male rat hepatocytes via oxidative dehalogenation and glutathione S-conjugation pathways.

In vitro metabolism of 1,2,3,3,3-pentafluoropropene (PFP) was investigated in the present study. PFP was metabolized via cytochrome P450-catalyzed oxidative dehalogenation in liver microsomes and glutathione transferase (GST)-catalyzed conjugation in liver microsomes and cytosol. Two oxidation products, 2,3,3,3-tetrafluoropropionaldehyde (TPA) and 3,3,3-trifluoropyruvaldehyde (TFPA), and two GSH conjugates, S-(2,3,3,3-tetrafluoropropenyl)-GSH (TFPG) and S-(1,2,3,3,3-pentafluoropropyl)-GSH (PFPG) were identified. Enzyme kinetic parameters for the formation of TFPA, TFPG, and PFPG were obtained in male and female rat, mouse, dog, and human liver microsomes and cytosol and were confirmed using freshly isolated male rat hepatocytes. For the TFPA pathway, dog microsomes exhibited much larger K(m) values than rat, mouse, and human microsomes. Sex differences in the rates of metabolism within a given species were minor and generally were less than 2-fold. Across the species, liver microsomes were the primary subcellular fraction for GSH S-conjugation and the apparent reaction rates for the formation of TFPG were much greater than those for PFPG in liver microsomes. PFPG was unstable and had a half-life of approximately 3.9 h in a phosphate buffer (pH 7.4 and 37°C). The intrinsic clearance values for the formation of TFPA were much greater than those for the formation of GSH S-conjugates, suggesting that cytochrome P450-mediated oxidation is the primary pathway for the metabolism of PFP at relatively low PFP concentrations. Because saturation of the GST-mediated reactions was not reached at the highest possible PFP concentration, GSH S-conjugation may become a much more important pathway at higher PFP concentrations (relative to the K(m) for TFPA).

Comorbidities and factors related to discontinuation of pharmacotherapy among outpatients with major depressive disorder.

OBJECTIVE: Although many studies have researched adherence to pharmacotherapy among patients with major depressive disorder (MDD), the effects of chronic depression, anxiety comorbidities, migraine, and other factors on adherence have rarely been studied. This study investigated which comorbidities and factors independently predicted discontinuation of pharmacotherapy among psychiatric outpatients with MDD. METHODS: One hundred thirty-five subjects (34 men, 101 women) with MDD were enrolled. MDD and anxiety comorbidities were diagnosed using the Structured Clinical Interview for DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision), migraine was diagnosed based on the International Classification of Headache Disorders, 2nd Edition, and depression severity was evaluated using the Hamilton Depression Rating Scale. Six months later, subjects' reasons for discontinuation were investigated, and Cox proportional hazards regression and logistic regression were used to investigate the independent factors predicting discontinuation. RESULTS: Subjects with chronic depression, migraine, panic/agoraphobia, or posttraumatic stress disorder attended follow-up for longer before discontinuation than those without. Chronic depression and greater age independently predicted a longer follow-up before discontinuation. Concern about and intolerance of the side effects of antidepressants and lack of insight into MDD independently predicted discontinuation within 2 months. "Self-reported recovery" was the most common reason for discontinuation; however, 53.8% of the subjects who cited this reason did not reach full remission. CONCLUSIONS: The impact of the duration of depression (chronic depression) on adherence may be more important than the severity of depression, anxiety comorbidities, and migraine. Education of MDD patients and society in general to improve understanding of MDD and antidepressants is needed to enhance adherence to pharmacotherapy.

Preventing the degradation of mps1 at centrosomes is sufficient to cause centrosome reduplication in human cells.

Supernumerary centrosomes promote the assembly of abnormal mitotic spindles in many human tumors. In human cells, overexpression of the cyclin-dependent kinase (Cdk)2 partner cyclin A during a prolonged S phase produces extra centrosomes, called centrosome reduplication. Cdk2 activity protects the Mps1 protein kinase from proteasome-mediated degradation, and we demonstrate here that Mps1 mediates cyclin A-dependent centrosome reduplication. Overexpression of cyclin A or a brief proteasome inhibition increases the centrosomal levels of Mps1, whereas depletion of Cdk2 leads to the proteasome-dependent loss of Mps1 from centrosomes only. When a Cdk2 phosphorylation site within Mps1 (T468) is mutated to alanine, Mps1 cannot accumulate at centrosomes or participate in centrosome duplication. In contrast, phosphomimetic mutations at T468 or deletion of the region surrounding T468 prevent the proteasome-dependent removal of Mps1 from centrosomes in the absence of Cdk2 activity. Moreover, cyclin A-dependent centrosome reduplication requires Mps1, and these stabilizing Mps1 mutations cause centrosome reduplication, bypassing cyclin A. Together, our data demonstrate that the region surrounding T468 contains a motif that regulates the accumulation of Mps1 at centrosomes. We suggest that phosphorylation of T468 attenuates the degradation of Mps1 at centrosomes and that preventing this degradation is necessary and sufficient to cause centrosome reduplication in human 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.

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.

The impact of anxiety and migraine on quality of sleep in patients with major depressive disorder.

OBJECTIVE: The aim of this study was to investigate the impact of anxiety disorders and migraine on sleep quality and to find the independent factors that predict sleep quality among patients with major depressive disorder (MDD). METHOD: Psychiatric outpatients diagnosed with MDD were enrolled in the study. Major depressive disorder and 7 anxiety disorders were diagnosed using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Migraine was diagnosed based on the International Classification of Headache Disorders, Second Edition. Headache intensity and frequency were reported by the subjects. The Pittsburgh Sleep Quality Index and Hamilton Depression Rating Scale were used to evaluate quality of sleep and depression severity, respectively. Multiple linear regressions were used to identify independent factors related to sleep quality. RESULTS: One hundred thirty-five subjects (34 men and 101 women) with MDD were enrolled in the study. Subjects with panic disorder and agoraphobia were found to have poorer Pittsburgh Sleep Quality Index scores. Subjects with panic disorder, agoraphobia, and migraine had higher scores for items relating to sleep quality in the Hamilton Depression Rating Scale. Headache intensity and frequency correlated with sleep disturbance. Panic disorder was independently predictive of poor sleep quality. Both migraine and panic disorder independently predicted a greater severity of depression. CONCLUSION: Our study demonstrates the negative impact of panic disorder and migraine on MDD and some of the interrelations between depression, anxiety, and sleep quality. Future studies should further explore these interactions and consider possible therapeutic interventions.

Liver microsomes and S9 from rainbow trout (Oncorhynchus mykiss): comparison of basal-level enzyme activities with rat and determination of xenobiotic intrinsic clearance in support of bioaccumulation assessment.

Metabolism plays an important role in bioaccumulation of xenobiotics in fish. The applicability of trout liver microsomes and S9 fraction in bioaccumulation assessment of xenobiotics in fish was investigated in the present study. Basal-level activities of 7-ethoxyresorufin-O-dealkylase, testosterone 6beta-hydroxylase, glutathione-S-transferase, and uridine 5'-diphospho-glucuronosyltransferase in trout liver microsomes and S9 were significantly lower than those in rat liver microsomes and S9. The in vitro-to- in vivo scaling factors, which are the values of liver microsomal and S9 protein contents per unit weight of trout liver, were determined to be 38.4 +/- 5.1 (mean +/- standard deviation throughout) and 95.9 +/- 11.9 mg/g, respectively. Intrinsic clearance (CL(int)) values for a number of reference compounds obtained from trout liver S9 were lower than those from trout liver microsomes. After correction with the scaling factors, trout liver microsomes and S9 provided equivalent prediction of trout hepatic clearance (CL(H)) using the well-stirred liver model, but their CL(H) values were significantly lower than those obtained from freshly isolated trout hepatocytes. Consequently, trout liver microsomes and S9 showed poorer prediction of the bioconcentration factors of the reference compounds compared with trout hepatocytes. Unit conversion revealed that CL(int) values obtained from trout liver microsomes and S9 were 6.3 to 22.4% of those from trout hepatocytes, which explained, to a large extent, the differences in their CL(H) and bioconcentration factor prediction.

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 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.

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.