Pectoralis Major Muscle Flap Utilization in Salvage Esophagectomy Including Great Vessel Resection Reconstructed by Prosthetic Grafts.

BACKGROUND: Salvage surgery is a therapeutic option for recurrent or residual esophageal cancer after definitive chemoradiation therapy. This report aimed to describe the procedure of reconstruction after salvage esophagectomy involving great vessel resection using prosthetic grafts, a pectoralis major muscle (PM) flap, and free jejunal transfer, if required. To the best of our knowledge, no previous report has described the reconstruction of the defect after combined esophageal and great vessel resection. PATIENTS AND METHODS: From January 2017 to December 2022, 4 patients underwent salvage esophagectomy with excision of the great vessels and reconstruction with prosthetic grafts, as well as a PM flap placement in a single center. We retrospectively investigated the patients' clinical data. The patients were all men, with a median age of 70 (range, 67-77) years. Regarding neoadjuvant therapy, 2 patients received chemoradiation therapy, 1 patient received radiotherapy only due to drug-induced pneumonia, and 1 patient received chemotherapy with adjuvant radiotherapy. RESULTS: Alimentary tract reconstruction was performed by free jejunal transfer in 2 cases, direct suture in 1 case, and stomach roll in 1 case. In all cases, a vascular bypass was established before tumor resection. We created mediastinal tracheostoma in 2 cases. A PM flap was inserted to cover the prosthetic grafts and approximate the tracheal mucosa. With regard to major complications, leakage from the jejunal esophageal anastomotic site was observed in 2 cases. The leakage improved with conservative treatment without graft removal or replacement in both cases. CONCLUSIONS: In cases of locally recurrent or residual tumors after definitive chemoradiation therapy, salvage esophagectomy along with great vessel resection, followed by reconstruction using prosthetic grafts, PM flaps, and free jejunal transfer, if necessary, is a useful option.

Urine autotaxin levels reflect the disease activity of sarcoidosis.

Since the clinical outcome of patients with sarcoidosis is still unpredictable, a good prognostic biomarker is necessary. Autotaxin (ATX) and phosphatidylserine-specific phospholipase A1 (PS-PLA1) function as main enzymes to produce lysophospholipids (LPLs), and these enzymes are attracting attention as useful biomarkers for several chronic inflammatory diseases. Here, we investigated the relationships between LPLs-producing enzymes and the disease activity of sarcoidosis. In total, 157 patients with sarcoidosis (active state, 51%) were consecutively enrolled. Using plasma or urine specimens, we measured the values of LPLs-producing enzymes. Urine ATX (U-ATX) levels were significantly lower in the active state compared to those in the inactive state, while the plasma ATX (P-ATX) and PS-PLA1 levels showed no significant difference between these two states. Concerning the comparison with existing clinical biomarkers for sarcoidosis, U-ATX showed a weak negative correlation to ACE, P-ATX a weak positive correlation to both ACE and sIL-2R, and PS-PLA1 a weak positive one to sIL-2R. Notably, only the U-ATX levels inversely fluctuated depending on the status of disease activity whether OCS had been used or not. These findings suggest that U-ATX is likely to be a novel and useful molecule for assessing the disease activity of sarcoidosis.

Physical and chemical properties of nabak (Zizyphus spina-christi) seed kernel and sweet pepper (Capsicum annuum L.) seed oils.

BACKGROUND: Nabak seed kernels and sweet pepper seeds, which are separated from the fruits and discarded as waste after processing or consumption, contain high levels of oils (30.19% and 19.57%, respectively). The chemical and thermal characteristics of nabak seed kernel oil (NSO) and sweet pepper seed oil (PSO) were investigated in this study. RESULTS: The NSO and PSO contained high levels of unsaturated fatty acids (84.1% and 86.5%, respectively), and the major fatty acid was oleic acid (57.3%) in NSO, but it was linoleic acid (69.4%) in PSO. The triacylglycerol (TAG) profiles show that NSO contained ten TAG species, three of which represented 87.1%, namely C54:3, C52:2 and C54:4, and triolein was the dominant (OOO, 47.0%). Pepper seed oil contained nine TAG molecular species, four of which represented 93.6%, namely C54:6, C52:4, C54:4 and C52:5, and trilinolein was dominant (LLL, 44.0%). The differential scanning calorimetry (DSC) analysis of NSO revealed that three exothermal peaks were detected during cooling, two endothermal peaks were detected during melting, and the major peak occurred at a low temperature. For PSO, three exothermal peaks were detected during cooling, three peaks were detected (one of them was exothermal) during melting, and the major peaks were observed at low temperatures. Fourier transform infrared (FTIR) spectra indicated that NSO and PSO did not contain peroxides or trans fatty acids, but they did contain low concentrations of free fatty acids. CONCLUSION: This study offers a scientific basis for the use of NSO and PSO as new sources of edible oils for food applications. © 2021 Society of Chemical Industry.

Crystallization and melting properties studied by DSC and FTIR spectroscopy of goldenberry (Physalis peruviana) oil.

The chemical and thermal characteristics of goldenberry pomace oil (GPO) and goldenberry seed oil (GSO) were investigated. GPO and GSO contained high levels of unsaturated fatty acids (90.1% and 85.1%, respectively), and the major fatty acid was linoleic (62.0% and 72.8%, respectively). Additionally, GPO contained eleven triacylglycerol (TAG) species, three of which represented 82.7%, namely C54:6, C54:4 and C52:4, and trilinolein was the dominant one (35.5%). GSO contained nine TAG species, two of which represented 80.3%, namely C54:6 and C52:4, and trilinolein was dominant (53.3%). The DSC analysis of GPO and GSO revealed that three exothermal peaks were detected during cooling. Three endothermal peaks (one of which is exothermal for GSO) were detected during melting, and the most significant peaks occurred at low temperatures. FTIR spectra indicated that GPO and GSO did not contain peroxides or trans fatty acids, but they did contain low concentrations of free fatty acids.

Unexpectedly rigid short peptide foldamers in which NH-π and CH-π interactions are preserved in solution.

NH-π and CH-π interactions, due to their weak character, are not easily identified in solution. We report a group of isolable short peptides with stable folds, in which NH-π and CH-π main chain-side chain interactions can be detected in solution by means of NMR and ATR-IR spectroscopy.

Effects of indacaterol on the LPS-evoked changes in fluid secretion rate and pH in swine tracheal membrane.

An acquired dysregulation of airway secretion is likely involved in the pathophysiology of chronic bronchitis and chronic obstructive pulmonary disease (COPD). Nowadays, it is widely known that several kinds of long-acting bronchodilators reduce the frequency of COPD exacerbations. However, limited data are available concerning the complementary additive effects on airflow obstruction. Using an optical method and a selective pH indicator, we succeeded in evaluating the gland secretion rate and the pH in swine tracheal membrane. A physiologically relevant concentration of acetylcholine (ACh) 100 nM induced a gradual increase in the amount of gland secretion. Lipopolysaccharides (LPS) accelerated the ACh-induced secretory responses up to around threefold and lowered the pH level significantly. Long-acting ß2-agonists (LABAs) including indacaterol (IND), formoterol, and salmeterol restored the LPS-induced changes in both the hypersecretion and acidification. The subsequent addition of the long-acting muscarine antagonist, glycopyrronium, further increased the pH values. Two different inhibitors for cystic fibrosis transmembrane conductance regulator (CFTR), NPPB and CFTRinh172, abolished the IND-mediated pH normalization in the presence of both ACh and ACh + LPS. Both immunofluorescence staining and western blotting analysis revealed that LPS downregulated the abundant expression of CFTR protein. However, IND did not restore the LPS-induced decrease in CFTR expression on Calu-3 cells. These findings suggest that the activation of cAMP-dependent HCO3- secretion through CFTR would be partly involved in the IND-mediated pH normalization in gland secretion and may be suitable for the maintenance of airway defense against exacerbating factors including LPS.

The Clinical Features of Patients with Sarcoidosis and Malignant Diseases in Japan.

Objective Recent studies suggest a significant association between sarcoidosis and malignancy, although the results have remained controversial. The aim of this study is to evaluate the clinical features of patients with sarcoidosis associated with malignant diseases in Japan. Patients We conducted a medical record review of all sarcoidosis patients in Tohoku University Hospital between January 1, 1981, and May 31, 2017. Methods The clinical records and pathology reports for each patient were screened, and the clinical characteristics of malignancies as well as sarcoidosis were reviewed. Results A total of 52 (18.8%) patients with malignancy were identified among 277 patients with sarcoidosis. Among those 52 patients, we identified 62 with malignant diseases. These patients were older and more likely to be women than the remaining 225 (81.2%) sarcoidosis patients without malignancy. The most prevalent malignant disease was breast cancer (14 cases, 22.6%), followed by stomach cancer (8 cases, 12.9%) and lung cancer (7 cases, 11.3%). Among the 14 patients with both sarcoidosis and breast cancer, 8 (57.1%) were diagnosed with breast cancer before sarcoidosis. All of these eight cases had undergone surgical resection of the cancer. Conclusion This study showed a higher incidence of patients with both sarcoidosis and malignancy in Japan than in some western countries. Breast cancer is the most prevalent malignant disease. The high frequency of sarcoidosis after surgical resection of breast cancer may suggest a causative association between malignancy and the development of sarcoidosis.

[Elements that cancer peer supporters working in Japanese hospitals consider to be important in helping them perform their role].

Objectives　The purpose of this study was to identify elements that cancer peer supporters working in Japanese hospitals consider to be important in helping them perform their role.Methods　A qualitative inductive research was conducted. Introductions to potential participants were obtained from a patient association that agreed to help with the study. Interviews were conducted from July through October 2014, using an interview guide, with cancer peer supporters who consented to participate in the study. Elements they perceived as important to the performance of their role were inductively identified from interview transcripts. The analysis consisted of coding phrases in the text and organizing the codes generated into categories and subcategories.Results　The study participants consisted of 10 cancer peer supporters (2 men, 8 women), in the age range of 40 to 70 years, who provided private counseling and worked in cancer support groups in hospitals. The analysis generated 129 codes, 11 subcategories, and 5 categories. These 5 categories were: [1.Help service users determine their own paths by listening to and accepting what they say with a non-judgmental attitude]; [2.Offer a perspective distinct from that of the medical staff]; [3.Think of ways to achieve a good balance between one's personal life and cancer peer support work while maintaining a stable state of mind]; [4.Ensure that one maintains the necessary knowledge and skills, and continually improve oneself]; and [5.Build relationships of trust with medical staff and the hospital].Conclusion　Category [1] and category [2] were behaviors regarded as important when interacting with users. They were "matters regarded as important during the practice of cancer peer support working for users," and comprised the core of matters that were regarded as important. Next, as for matters regarded as important in relation to the supporters themselves, the categories were [3] and [4]. These were "matters regarded as important for continuity and qualitative improvement of cancer peer support working." Areas that call for improvement in relation to this are preparation of support systems and learning environments. Another matter regarded as important was category [5]. This was a "matter regarded as important to smoothen and facilitate cancer peer support working." Placing importance on relationships of trust with medical staff and hospitals could be considered a distinctive characteristic of cancer peer supporters working at hospitals.

Overall Shape Constraint of Alternating α/ß-Hybrid Peptides Containing Bicyclic ß-Proline.

Our NMR, IR/Raman, CD spectroscopic, and X-ray crystallographic studies, as well as accelerated molecular dynamics simulations, showed that alternating hybrid α/ß-peptides containing a bicyclic ß-proline surrogate form unique extended curved folds, regardless of the peptide length and solvent environment. It is suggested that extended ß/PPII structures are preferred in the insulating α-alanine moieties between the rigid bicyclic ß-proline structures. These hybrid peptides inhibit p53-MDM2 and p53-MDMX protein-protein interactions.

Melatonin is a potential drug for the prevention of bone loss during space flight.

Astronauts experience osteoporosis-like loss of bone mass because of microgravity conditions during space flight. To prevent bone loss, they need a riskless and antiresorptive drug. Melatonin is reported to suppress osteoclast function. However, no studies have examined the effects of melatonin on bone metabolism under microgravity conditions. We used goldfish scales as a bone model of coexisting osteoclasts and osteoblasts and demonstrated that mRNA expression level of acetylserotonin O-methyltransferase, an enzyme essential for melatonin synthesis, decreased significantly under microgravity. During space flight, microgravity stimulated osteoclastic activity and significantly increased gene expression for osteoclast differentiation and activation. Melatonin treatment significantly stimulated Calcitonin (an osteoclast-inhibiting hormone) mRNA expression and decreased the mRNA expression of receptor activator of nuclear factor κB ligand (a promoter of osteoclastogenesis), which coincided with suppressed gene expression levels for osteoclast functions. This is the first study to report the inhibitory effect of melatonin on osteoclastic activation by microgravity. We also observed a novel action pathway of melatonin on osteoclasts via an increase in CALCITONIN secretion. Melatonin could be the source of a potential novel drug to prevent bone loss during space flight.

Characterization of the Ca2+-coordination structures of L- and T-plastins in combination with their synthetic peptide analogs by FTIR spectroscopy.

FTIR spectroscopy was employed to characterize the coordination structures of divalent cations (M2+ = Ca2+ or Mg2+) bound by L- and T-plastins, which contain two EF-hand motifs. We focused on the N-terminal headpieces in the L- and T-plastins to analyze the regions of COO- stretching and amide-I in solution. The spectral profiles indicated that these headpieces have EF-hand calcium-binding sites because bands at 1551 cm-1 and 1555 cm-1 were observed for the bidentate coordination mode of Glu at the 12th position of the Ca2+-binding site of Ca2+-loaded L-plastin and T-plastin, respectively. The amide-I profile of the Mg2+-loaded L-plastin headpiece was identical with that of the apo L-plastin headpiece, meaning that L-plastin has a lower affinity for Mg2+. The amide-I profiles for apo, Mg2+-loaded and Ca2+-loaded T-plastin suggested that aggregation was generated in protein solution at a concentration of 1 mM. The implications of the FTIR spectral data for these plastin headpieces are discussed on the basis of data obtained for synthetic peptide analogs corresponding to the Ca2+-binding site.

Coordination to Divalent Cations by Calcium-Binding Proteins.

Fourier-transform infrared spectroscopy (FTIR) is a powerful tool for examining the metal coordination of the side chain COO- groups of Glu and Asp on Ca2+-binding proteins in solution. The behavior of COO- symmetric stretch can be investigated by using protein samples in H2O solution. However, it is difficult to obtain information about the behavior of the COO- antisymmetric stretch in H2O solution, because the COO- antisymmetric stretching band overlaps with the amide II band. Therefore, to obtain reliable infrared spectra in the region of COO- antisymmetric stretch, exchangeable protons in the protein should be completely deuterated by incubating the apoprotein dissolved in D2O under mild heating conditions.

Application of C-Terminal 7-Azabicyclo[2.2.1]heptane to Stabilize ß-Strand-like Extended Conformation of a Neighboring α-Amino Acid.

ß-Strands are formed by extended linear peptide chains that are usually paired to form ß-sheet structure through interstrand hydrogen bonding. Linking a structured organic molecule with α-amino acid(s) can enforce or stabilize ß-strand-like extended structures of the jointed amino acids. Spectroscopic and simulation studies indicated that the presence of a C-terminal 7-azabicyclo[2.2.1]heptane amine (Abh) favors a ß-strand-like extended conformation of the adjacent α-amino acid on the N side. The bridgehead substitution of the Abh unit biases the amide cis-trans equilibrium of the adjacent α-amino acid residue to cis conformation. The proximity, specified by the presence of bond paths (such as H-H bond path) between the bridgehead proton of Abh and the α-proton of the α-amino acid provides a driving force favoring the extended conformation, which is independent of solvents. These results provide a basis for de novo design of ß-strand-mimicking extended peptides by using ß-strand enforcer/stabilizer even in the absence of the interstrand hydrogen bonding.

TLR7 agonist attenuates acetylcholine-induced, Ca2+ -dependent ionic currents in swine tracheal submucosal gland cells.

NEW FINDINGS: What is the central question of this study? Does Toll-like receptor 7 (TLR7) have any direct effects on Ca2+ -dependent physiological function of tracheal submucosal gland cells? What is the main finding and its importance? TLR7 is co-localized with SERCA2 in tracheal submucosal gland cells and causes a rapid attenuation of acetylcholine (ACh)-induced, Ca2+ -dependent ionic currents through the activation of SERCA2-dependent Ca2+ clearance. TLR7 is abundantly expressed in the airways of both swine and healthy human subjects, but is significantly downregulated in chronic obstructive pulmonary disease (COPD) airways. These findings suggest that a dysfunction of TLR7 in COPD removes the brake on ACh-induced serous secretion during viral infections, resulting in prolonged airway hypersecretion, and that it is one of the triggers of COPD exacerbations. ABSTRACT: Airway surface fluids are mainly secreted from submucosal glands (SMGs) and play important roles in the defence of airways via the activation of mucociliary transport. Toll-like receptor 7 (TLR7) recognizes and eliminates single stranded RNA (ssRNA) viruses through the induction of innate immunity. However, there is no obvious connection between TLR7 and mucus secretion, aside from TLR7 recognizing ssRNA viruses, which are often associated with airway hypersecretion in chronic obstructive pulmonary disease (COPD). Here, we investigated whether TLR7 has any direct effects on the Ca2+ -dependent physiological function of tracheal SMG cells. Patch-clamp analyses revealed that TLR7 ligand inhibited the acetylcholine (ACh)-induced ionic currents in isolated tracheal SMG cells. Intracellular calcium assays and pharmacological analyses revealed that TLR7 attenuated the transient rises in the intracellular calcium concentration evoked by ACh by activating sarco/endoplasmic reticulum Ca2+ -ATPase 2 (SERCA2). Immunofluorescence staining and immunohistochemical staining revealed that TLR7 was co-localized with SERCA2. These findings suggest that the activation of TLR7 during viral infections contributes to the rapid attenuation of ACh-induced ionic currents through an increase in SERCA2-dependent Ca2+ clearance in healthy airway SMG cells. Our study also revealed that TLR7 expression was significantly downregulated in COPD airways. Based on these findings, we speculate that a dysfunction of TLR7 may not only have an adverse effect on the elimination of these viruses but also remove the brake on ACh-induced serous secretion, resulting in prolonged hypersecretion and acting as one of the triggers of COPD exacerbations.

[Support that cancer peer supporters working at medical institutions currently receive and the support they actually need].

Objectives　This research aims to ascertain the kinds of support cancer peer supporters at medical institutions currently receive and the support they actually need.Methods　Participants in the study were ten cancer peer supporters who were recommended by a patient association and who agreed to participate in the study. Using a qualitative descriptive method, interviews were conducted using an interview guide from July to October 2014. Codes were extracted from the interview transcript and divided into categories and subcategories. Accuracy was ensured by checking the data with the participants. The study was conducted with the approval of the Ethics Committee of Mejiro University.Results　Research participants consisted of two men and eight women aged forty to seventy years, who were private counselors, telephone counselors, or members of cancer salons at hospitals. Four categories were generated on the basis of the support that cancer peer supporters are currently receiving: mutual learning and support among peer supporters, learning and encouragement from patients, self-improvement in peer supporters, and cooperation with hospitals and the government. Seven categories were generated on the basis of the support that cancer peer supporters need: opportunities for peer supporters to learn from and support each other, further studies on cancer peer support, reliable and up-to-date information, society's understanding and cooperation regarding cancer, financial support for support activities and patient associations, improvement of cancer peer support system, and quality assurance of peer supporter training courses.Conclusion　Cancer peer supporters were supporting each other, gaining encouragement from patients, improving themselves, and gaining support from others. However, they also needed additional assistance such as opportunities for supporters to learn from and support each other and reliable and up-to-date information. Moreover, peer supporters needed advice and emotional support from hospital staff as they experienced difficulties during consultation. Various other types of support were needed, such as society's understanding and cooperation regarding cancer, financial support for support activities and patient associations, institutionalization of peer supporter placement in hospitals, and quality assurance of peer supporter training courses. Overall, support for cancer peer supporters is still not sufficient; thus, further help is necessary.

Simultaneous development of sarcoidosis and cutaneous vasculitis in a patient with refractory Crohn's disease during infliximab therapy.

BACKGROUND: Paradoxical inflammations during anti-TNF-α therapy are defined as adverse effects such as psoriasiform skin lesions, uveitis and sarcoidosis-like granulomas induced by immune reactions, not by infectious agents. Here, we report a very rare case of the simultaneous development of sarcoidosis and cutaneous vasculitis in a patient with refractory Crohn's disease during infliximab therapy and both of which resolved spontaneously without the cessation of infliximab. CASE PRESENTATION: In September 2000, 23-year old Japanese male was diagnosed with Crohn's disease. Prednisolone in combination with mesalazine was introduced at first and succeeded for almost one year. In June 2002, since his gastrointestinal symptoms relapsed and were refractory, infliximab (IFX) therapy 5 mg/kg was introduced. In February 2011, because he had repeated arthralgia almost every intravenous IFX administration, IFX was increased to 10 mg/kg under the diagnosis of a secondary failure of IFX. In December 2012, he complained of slight dry cough and an itchy eruption on both lower limbs, and he was referred to our hospital due to the appearance of bilateral hilar lymphadenopathy on chest X-ray examination. Chest computed tomogram revealed bilateral hilar lymphadenopathy and fine reticulonodular shadows on the bilateral upper lungs. Serum calcium, angiotensin-converting enzyme and soluble interleukin 2 receptor levels were not elevated, but the titer of antinuclear antibody was considerably elevated. Mycobacterium infection was carefully excluded. Trans-bronchial lung biopsy showed non-caseating epithelioid cell granulomas compatible with sarcoidosis. The skin biopsy of the right limb was diagnosed as leukocytoclastic vasculitis. The patient was diagnosed as having a series of paradoxical inflammations during anti-TNF-α therapy. Since his paradoxical inflammations were not severe and opportunistic infections were excluded, IFX was cautiously continued for refractory Crohn's disease. Nine months later, not only his intrathoracic lesions but also his cutaneous lesions had spontaneously resolved. CONCLUSION: Physicians caring for patients with anti-TNF-α therapy should know that, based on a careful exclusion of infectious agents and thoughtful assessment of the patient's possible risks and benefits, paradoxical inflammations can be resolved without the cessation of anti-TNF-α therapy.

Treatment of posttraumatic stress disorder using the traditional Japanese herbal medicine saikokeishikankyoto: a randomized, observer-blinded, controlled trial in survivors of the great East Japan earthquake and tsunami.

The Great East Japan earthquake and tsunami caused immense damage over a wide area of eastern Japan. Hence, many survivors are at high risk for posttraumatic stress disorder (PTSD). This randomized, observer-blinded, controlled trial examined the efficacy and safety of the traditional Japanese herbal formula saikokeishikankyoto (SKK) in the treatment of PTSD among survivors of this disaster. Forty-three participants with an Impact of Event Scale-Revised (IES-R) score ≥ 25 were randomized into SKK (n = 21) and control (n = 22) groups. The primary endpoint was the change in IES-R scores from baseline till after 2 weeks of treatment. Intergroup statistical comparisons were performed. The magnitude of changes in total IES-R scores differed significantly between the two groups (P < 0.001). Post hoc analysis showed that the total IES-R score improved significantly in the SKK group from 49.6 ± 11.9 to 25.5 ± 17.0 (P < 0.001). Subscale scores improved significantly in the SKK group (avoidance, P = 0.003; hyperarousal, P < 0.001; intrusion, P < 0.001). Two-week treatment with SKK significantly improved IES-R scores among PTSD patients. This traditional medicine may be a valid choice for the treatment of psychological and physical symptoms in PTSD patients.

The clinical utility of makeshift beds in disaster shelters.

OBJECTIVE: Strong earthquakes have been reported to increase the incidence of diseases. One reason for these increases may be the stress from the poor living environment for evacuees in disaster shelters. To reduce stress, makeshift cardboard beds were introduced in shelters in the Ishinomaki region, one of the areas heavily damaged by the Great East Japan Earthquake, 4 months after the earthquake. The study was performed to determine whether use of the beds offered a reduction in the disease burden. METHODS: Blood pressure and blood D-dimer values, often used as diagnostic tests for venous thrombosis, were checked. The timed Up & Go (TUG) test, which assesses functional mobility; a questionnaire survey about symptoms (cough, insomnia, and lumbago); and an SF-8 health survey, a health-related quality of life survey, were also administered before and 1 month after introducing the beds. RESULTS: Blood pressure measurements, TUG test results, and questionnaire survey scores improved significantly 1 month after the introduction of the beds. Also, evacuees with higher blood D-dimer values tended to show improvement, suggesting that the beds may have had a good effect on persons with underlying venous thrombotic disorders. CONCLUSION: Makeshift beds of cardboard could be very useful in disaster shelters.