Ensuring continuous TB treatment across Asian borders.

BACKGROUND: Mid-treatment cross-border migration of patients with TB increases the risk of treatment interruption. OBJECTIVE: To establish a cross-border referral process for patients with TB in Japan, and enhance their access to health facilities and treatment outcomes. DESIGN: This prospective cohort study describes and assesses the process of foreign-born patients with TB who returned to their home countries during treatment, focusing on their access to healthcare facilities and treatment outcomes. RESULTS: We enrolled 135 foreign-born patients with TB, and confirmed that 112 (83.0%) were referred to and accessed healthcare facilities after returning to their home countries. Of 102 patients due to complete treatment as of July 2023, 87 (85.3%) completed their treatment. We did not identify significant differences in the treatment success rate among patient characteristics, except between the patients with confirmed access to a healthcare facility and those without (P < 0.001). We confirmed that 49/87 (56.3%) patients had completed treatment with official data. CONCLUSION: The access and treatment success rates of the cross-bordered patients with TB from Japan were >80%; however, we should further improve this proportion by confirming the treatment outcomes with official data.

CONTEXTE: La migration transfrontalière en milieu de traitement des patients atteints de TB augmente le risque d'interruption du traitement. OBJECTIF: Etablir un processus d'orientation transfrontalière pour les patients atteints de TB au Japon et à améliorer leur accès aux établissements de santé et les résultats de leur traitement. CONCEPTION: Cette étude de cohorte prospective décrit et évalue le processus des patients atteints de TB et nés à l'étranger qui sont retournés dans leur pays d'origine pendant le traitement, en se concentrant sur leur accès aux établissements de santé et sur les résultats du traitement. RÉSULTATS: Nous avons recruté 135 patients atteints de TB et nés à l'étranger et confirmé que 112 (83,0%) ont été orientés vers des établissements de santé et y ont accédé après leur retour dans leur pays d'origine. Des 102 patients qui devaient terminer leur traitement en juillet 2023, 87 (85,3%) l'ont terminé. Nous n'avons pas identifié de différences significatives dans le taux de réussite du traitement en fonction des caractéristiques des patients, sauf entre les patients ayant un accès confirmé à un établissement de santé et ceux qui n'en ont pas (P < 0,001). Nous avons confirmé que 49 (56,3%) des 87 patients avaient terminé leur traitement à l'aide des données officielles. CONCLUSION: Les taux d'accès et de réussite du traitement des patients transfrontaliers atteints de TB en provenance du Japon étaient >85% ; cependant, nous devrions encore améliorer cette proportion en confirmant les résultats du traitement à l'aide de données officielles.

Middle-ear carcinoid tumour metastasising to the parapharyngeal space and the parotid gland.

Background. Middle-ear carcinoid tumour is a rare malignant tumour with an indolent course occasionally causing regional or distant metastasis. This paper presents a case of middle-ear carcinoid tumour metastasising to the parapharyngeal space and the parotid gland 20 years after the first surgery.Case report. A 35-year-old woman who underwent multiple tympanomastoidectomies for middle-ear carcinoid presented with tumours of both the parapharyngeal space and parotid gland, detected by regular imaging. Based on the clinical course, metastatic relapse of middle-ear carcinoid was suspected. This was treated with subtotal parotidectomy with elective neck dissection (levels II and III), leading to the pathological diagnosis of carcinoid tumour. A cervico-parotid approach was selected to avoid complications associated with parapharyngeal space tumour removal. Transient facial palsy (House-Brackmann grade III) occurred, which completely recovered two months after surgery.Conclusion. Awareness of parapharyngeal space tumours possibly caused by metastasis from a middle-ear tumour is necessary.

Formation of NaCl-type monodeuteride LaD by the disproportionation reaction of LaD2.

Previous x-ray diffraction measurements revealed the pressure-induced decomposition of an fcc LaH2.3 into H-rich and H-poor fcc phases around 11 GPa. The present neutron diffraction measurements on LaD2 confirm the formation of NaCl-type LaD as a counterpart of the D-rich LaD2+δ by disproportionation. First-principles enthalpy and lattice dynamic calculations demonstrate that the NaCl-type LaH is stabilized at high pressures and can be recovered at ambient conditions. Finding the NaCl-type LaH will pave the way for investigations on the site-dependent nature of hydrogen-metal interactions.

[Cardiac surgery for patients with ventricular dysfunction].

Coronary artery disease and aortic stenosis/regurgitation may cause irreversible myocardial damage, resulting in significant heart failure. Although the ultimate treatment of the end-stage heart failure is heart transplantation or ventricular assist devices, in most cases these patients still have some amount of functional and survival benefit by simple surgical treatment such as coronary artery bypass grafting (CABG) and valve replacement. However it is associated with significant perioperative mortality and morbidity.

Rocuronium priming for tracheal intubation in COVID-19 patients.

Priming doses of non-depolarising neuromuscular blocking drugs given before administration of anaesthetic agents have been used to hasten the onset of neuromuscular blockade. In the settings of coronavirus disease 2019 (COVID-19), this could be used to reduce the apnoeic, and potentially aerosol-generating, window. To our knowledge, we report the first cases of tracheal intubation with rocuronium for COVID-19 using the priming principle. Both patients needed their tracheas intubated for severe hypoxia using a rapid sequence induction technique with a priming dose of rocuronium. Despite adequate pre-oxygenation a sudden, unexpected fall in arterial oxygen saturations was observed in both patients after administration of a priming dose of 2 mg of rocuronium. Clinicians should consider this possible risk associated with priming doses of neuromuscular blocking drugs in the management of patients with respiratory failure due to COVID-19.

Transcription factor TFIIB sites important for interaction with promoter-bound TFIID.

Transcription initiation factor TFIIB recruits RNA polymerase II to the promoter subsequent to interaction with a preformed TFIID-promoter complex. The domains of TFIIB required for binding to the TFIID-promoter complex and for transcription initiation have been determined. The carboxyl-terminal two-thirds of TFIIB, which contains two direct repeats and two basic residue repeats, is sufficient for interaction with the TFIID-promoter complex. An extra 84-residue amino-terminal region, with no obvious known structural motifs, is required for basal transcription activity. Basic residues within the second basic repeat of TFIIB are necessary for stable interaction with the TFIID-promoter complex, whereas the basic character of the first basic repeat is not. Functional roles of other potential structural motifs are discussed in light of the present study.

Oral steroid decreases the progression of joint destruction of large joints in the lower extremities in rheumatoid arthritis.

To identify the risk factors for destruction of large joints in the lower extremities in patients with rheumatoid arthritis (RA) during a 4-year follow-up period in a prospective study.We enrolled consecutive patients who participated in both 2012 and 2016. Clinical data, disease activity, and types of medication were collected in 2012. Standard anteroposterior radiographs of weight-bearing joints (hips, knees, and ankles) were taken in 2012 and 2016. Radiographic progression was defined as progression in the Larsen grade or the need for joint arthroplasty or arthrodesis. The association between baseline characteristics and the incidence of radiographic progression was statistically assessed.A total of 213 patient were enrolled, and, after exclusion, 186 patients were analyzed. Sixty 9 patients (37.1%) showed radiographic progression in 1 of the large joints in the lower extremities. Multivariate regression analysis showed that radiographic progression was associated with older age, higher disease activity, and the presence of radiographic destruction at the baseline. The lower dosage of oral prednisolone was a significant risk factor compared with higher dosage when used.Patients with the risk factors should be followed closely to limit the progression of large joint destruction in the lower extremities.

Distinct biomarkers for different bones in osteoporosis with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is known to cause secondary osteoporosis and fragility fractures. This study aimed to identify biomarkers predictive of bone mineral density (BMD) change at three anatomical sites in patients with RA. METHODS: We conducted a prospective longitudinal study in patients with RA. In 2012, we recruited 379 patients from an RA cohort, 329 of whom underwent evaluation of blood and urine biomarkers together with measurement of BMD in the lumbar spine, proximal femur, and distal forearm. The BMD in these three regions was reassessed in 2014. We performed multivariate linear regression analysis to identify those factors associated with BMD change. RESULTS: The averages of age, body mass index, and disease activity score in 28 joints (DAS28) at baseline were 63.2 (minimum to maximum, 32-85), 21.3 (12.3-30.0), and 3.2 (0.1-5.9), respectively. Univariate analysis showed that the annual BMD change was significantly associated with the use of steroid, bisphosphonate (BP) or vitamin D (VitD), and serum homocysteine in the lumber spine; DAS28, the use of BP or VitD, CRP, and anti-cyclic citrullinated peptide antibody (ACPA) in the proximal femur; and the dosage of MTX, the use of BP or VitD, and serum tartrate-resistant acid phosphatase 5b (TRACP-5b) in the distal forearm, respectively. CONCLUSIONS: Predictive biomarkers for BMD change in RA patients differ at each anatomical site. Practitioners should treat each anatomical site with different markers and prescribe osteoporosis drugs to prevent fractures for RA patients.

Correction of the disease phenotype in the mouse model of Stargardt disease by lentiviral gene therapy.

Autosomal recessive Stargardt disease (STGD1) is a macular dystrophy caused by mutations in the ABCA4 (ABCR) gene. The disease phenotype that is most recognized in STGD1 patients, and also in the Abca4-/- mouse (a disease model), is lipofuscin accumulation in retinal pigment epithelium. Here, we tested whether delivery of the normal (wt) human ABCA4 gene to the subretinal space of the Abca4 -/- mice via lentiviral vectors would correct the disease phenotype; that is, reduce accumulation of the lipofuscin pigment A2E. Equine infectious anemia virus (EIAV)-derived lentiviral vectors were constructed expressing either the human ABCA4 gene or the LacZ reporter gene under the control of the constitutive (CMV) or photoreceptor-specific (Rho) promoters. Abca4-/- mice were injected subretinally with 1 microl ( approximately 5.0 x 10(5) TU) of each EIAV vector in one eye at postnatal days 4 and 5. An injection of saline, an EIAV-null vector, or an uninjected contralateral eye served as a control. Mice were killed at various times after injection to determine photoreceptor (PR) transduction efficiency and A2E concentrations. EIAV-LacZ vectors transduced from 5 to 20% of the PRs in the injected area in mice. Most importantly, a single subretinal injection of EIAV-CMV-ABCA4 to Abca4-/- mouse eyes substantially reduced disease-associated A2E accumulation compared to untreated and mock-treated control eyes. Treated eyes of Abca4-/- mice accumulated 8-12 pmol per eye (s.d.=2.7) of A2E 1 year after treatment, amounts comparable to wt controls, whereas mock-treated or untreated eyes had 3-5 times more A2E (27-39 pmol per eye, s.d.=1.5; P=0.001-0.005). Although extrapolation to humans requires caution, the high transduction efficiency of both rod and cone photoreceptors and the statistically significant reduction of A2E accumulation in the mouse model of STGD1 suggest that lentiviral gene therapy is a potentially efficient tool for treating ABCA4-associated diseases.

AP214, an analogue of alpha-melanocyte-stimulating hormone, ameliorates sepsis-induced acute kidney injury and mortality.

Sepsis remains a serious problem in critically ill patients with the mortality increasing to over half when there is attendant acute kidney injury. alpha-Melanocyte-stimulating hormone is a potent anti-inflammatory cytokine that inhibits many forms of inflammation including that with acute kidney injury. We tested whether a new alpha-melanocyte-stimulating hormone analogue (AP214), which has increased binding affinity to melanocortin receptors, improves sepsis-induced kidney injury and mortality using a cecal ligation and puncture mouse model. In the lethal cecal ligation-puncture model of sepsis, severe hypotension and bradycardia resulted and AP214 attenuated acute kidney injury of the lethal model with a bell-shaped dose-response curve. An optimum AP214 dose reduced acute kidney injury even when it was administered 6 h after surgery and it significantly improved blood pressure and heart rate. AP214 reduced serum TNF-alpha and IL-10 levels with a bell-shaped dose-response curve. Additionally; NF-kappaB activation in the kidney and spleen, and splenocyte apoptosis were decreased by the treatment. AP214 significantly improved survival in both lethal and sublethal models. We have shown that AP214 improves hemodynamic failure, acute kidney injury, mortality and splenocyte apoptosis attenuating pro- and anti-inflammatory actions due to sepsis.

Thermus thermophilus TMY isolated from silica scale taken from a geothermal power plant.

AIMS: To identify an extreme thermophile, strain TMY, isolated from silica scale from the geothermal electric power plant and to examine microdiversity of Thermus thermophilus strains. MATERIALS AND RESULTS: The isolated strain TMY was identified by morphological, biochemical and physiological tests. Phylogenetic comparison of the strain and other Thermus strains with 16S rDNA analysis, RAPD and ERIC-PCR fingerprinting were performed. Strain TMY was closely related to strain which was isolated from a hot spring in New Zealand and shown to belong to the Japanese Thermus cluster. However, there were considerable genetic differences between strain TMY and other Thermus species using DNA fingerprinting. CONCLUSIONS: Based on morphological, physiological and genetic properties, strain TMY could be a strain of T. thermophilus. The distinct properties of strain TMY suggest that microdiversity of T. thermophilus strains should be considered. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this study have demonstrated genetic diversity within T. thermophilus strains, which were previously masked by an almost identical 16S rDNA sequence. RAPD and ERIC-PCR could be potential methods for distinguishing between Thermus strains.

Increased risk of exacerbating gastrointestinal disease among elderly patients following treatment with calcium channel blockers.

BACKGROUND AND OBJECTIVE: Calcium channel blockers (CCBs) have been widely used for the treatment of hypertension and angina pectoris. It is presumed that CCBs decrease the lower esophageal sphincter pressure and as a result, the risk of gastrointestinal disease may be increased. Since the prevalence of gastrointestinal diseases has increased in elderly patients, it is possible that treatment with CCBs may have contributed to this increase. Therefore, we considered that the risk of exacerbating gastrointestinal disease among elderly patients by CCBs can be estimated by using the prescription ratio of antisecretory drugs as an outcome. METHOD: We hypothesized that patients who are prescribed CCBs would increase the use of antisecretory drugs involving H(2)-receptor antagonists and proton pump inhibitors (PPIs). From January 2001 to December 2005, a dynamic retrospective cohort study was performed at three community pharmacies in Nagasaki city, Japan, to assess the use of antisecretory drugs following treatment with CCBs among elderly patients. The correlation of initiation of antisecretory drugs treatment to maintenance therapy with PPIs was determined by the Cox proportional hazards model. RESULTS: The proposed study includes 303 patients prescribed CCBs and 258 controls. During the study period, 138 patients prescribed CCBs and 66 controls were initiated by giving antisecretory drugs; the hazard ratio was 1.40 (95% confidence interval 1.21-1.63). Eighty two patients taking CCBs and 32 controls were initiated by the maintenance therapy with PPIs; the hazard ratio was 1.48 (95% confidence interval 1.21-1.83). CONCLUSION: Patients who simultaneously initiated the use of antisecretory drugs with CCBs could not be found. Therefore, antisecretory drugs have not been used to prevent the gastrointestinal diseases caused by CCBs. The results obtained in this study suggest that the risk of gastrointestinal disease could be increased by long-term treatment with CCBs for elderly patients.

Cervical chondroid chordoma in a Shetland sheep dog.

A spayed female Shetland sheep dog aged 12 years was presented for examination with ataxia and hindlimb paralysis. Extradural spinal cord compression was found at the level of vertebrae C6-C7 by radiography and myelocomputed tomography. A jelly-like mass (0.6 x 1.3 cm) was removed surgically. Histopathological findings were characterized by proliferation of vacuolated polygonal cells (physaliphorous cells) in a mucinous matrix and the presence of chondroid tissue shown immunohistochemically to express S-100. The physaliphorous cells were immunolabelled strongly for vimentin and S-100, and weakly for cytokeratin. A diagnosis of canine cervical chondroid chordoma was made. This is considered to be the first report of a chondroid chordoma originating from the cervical region of the spine in the dog.

Unilateral optical nerve hypoplasia in a Beagle dog.

Unilateral (left eye) optic nerve hypoplasia was detected in a six-month-old male Beagle dog. Vision testing indicated that the left eye had poor vision and testing the pupillary light reflex showed the left eye to have an absence of the afferent pathway of the reflex but it had a normal efferent pathway. Ophthalmoscopy revealed a small-sized optic disc, winding retinal artery and dilated retinal vasculature in the left globe. Electroretinography showed no abnormal findings even in the left globe. Histopathologically, the left optic nerve was markedly hypoplastic and was composed of sparse neural elements and a moderate amount of connective and glial tissues. In the retina of the left globe, the nerve fibre layer and the ganglion cell layer were reduced in thickness, although a small number of ganglion cells were still present. There were no abnormal findings detected in the right globe and the right optic nerve. The brain appeared normal macroscopically.

Identical biological effects of pancreatic glucagon and a purified moiety of canine gastric immunoreactive glucagon.

Because in the dog, the gastric fundus contains the largest amount of glucagon immunoreactivity (IRG), the IRG of mucosal scrapes of 105 canine stomachs was extracted by acid-ethanol and then precipitated by ether-ethanol. The IRG recovered was measured by antisera 30K, specific for glucagon and K-4023, which cross-reacts with glucagon-like immunoreactivity. Extracts of mucosa of stomach fundus were further purified by gel filtration on Bio-Gel P-30 in 3M acetic acid. One pooled fraction corresponding to marker pancreatic glucagon in its elution volume was then gel-filtered on Bio-Gel P-30 in 0.05 M NH(4)HCO(3) and yielded one IRG peak, which, however, showed three immunoreactive components on polyacrylamide disc gel electrophoresis in urea. In addition, antiserum K-4023 reacted more strongly with that peak than antiserum 30K indicating the presence of glucagon-like immunoreactivity in this fraction. Subsequent ion-exchange column chromatography on DEAE-Sephadex A-25 and then CM-Bio-Gel A allowed purification to a single protein band on disc gel electrophoresis reacting equally to both antisera 30K and K-4023. 1.5 mug of purified gastric glucagon was obtained and its biological effects were compared to those of pancreatic glucagon in isolated rat hepatocytes. When immuno-equivalent amounts (300-2,500 pg/ml) of either type of glucagon were used, the same biological responses with respect to glycogenolysis and gluconeogenesis as well as urea, lactate, and pyruvate production were observed. Liver cyclic AMP was also raised to the same extent by either one of these hormones. We conclude that this moiety of gastric IRG is apparently identical to pancreatic glucagon because (a) their molecular weights, elution properties in ion exchange chromatography, and their electrophoretic mobility are indistinguishable and (b) both hormones elicited identical biological effects in isolated rat hepatocytes.

An improved computer-aided diagnosis scheme using the nearest neighbor criterion for determining histological classification of clustered microcalcifications.

OBJECTIVES: Our purpose was to evaluate the potential usefulness of the nearest neighbor case which was assumed to be the similar case in a CAD scheme for determining the histological classification of clustered microcalcifications. METHODS: Our database consisted of current and previous magnification mammograms obtained from 93 patients before and after three-month follow-up examination. It included 11 invasive carcinomas, 19 noninvasive carcinomas of the comedo type, 25 non-invasive carcinomas of the noncomedo type, 23 mastopathies, and 15 fibroadenomas. Six objective features on clustered microcalcifications were first extracted from each of the current and the previous images. The nearest neighbor case was then identified by the Euclidean distance in the previous and current feature-space. The histological classification of an unknown new case in question was assumed to be the same as that of the nearest neighbor case which has the shortest Euclidean distance in our database. RESULTS: The classification accuracies were 90.9% for invasive carcinoma, 89.5% for noninvasive carcinoma of the comedo type, 96.0% for noninvasive carcinoma of the noncomedo type, 82.6% for mastopathy, and 93.3% for fibroadenoma. These results were substantially higher than those with our previous CAD scheme. CONCLUSION: The nearest neighbor criterion was useful in a CAD scheme for determining the histological classification.

Molecular mechanisms of hydroxyurea(HU)-induced apoptosis in the mouse fetal brain.

Hydroxyurea (HU), a potent mammalian teratogen, affects proliferating embryonic cells and inhibits DNA synthesis. The teratogenic potential of HU has been well known in experimental animals for several decades. In this study, we investigated molecular mechanisms of HU-induced apoptosis in the telencephalon of the fetal brain by exposing pregnant mice to HU on day 13 of gestation. The number of TUNEL-positive cells began to increase at 3 h, peaked at 12 h, and rapidly decreased at 24 h. Although changes of p53 mRNA expression were not observed by RT-PCR, a p53-positive reaction was detected immunohistochemically in the nuclei of neuroepithelial cells from 1 h to 6 h, and p53-protein expression was simultaneously identified by Western blot analysis. The expression of p53-target genes was detected at both the mRNA and protein. The mRNA levels of apotosis-related genes (fas, fasL, and bax) and cell cycle-related genes (mdm2 and p21) were significantly elevated, and the degree to and sequence in which these target genes expressed was similar to those for fas, fasL, mdm2 and p21. Flow-cytometric and Western blot analyses of cell cycle-related proteins suggested that neuroepithelial cells are arrested at the S checkpoint from 3 to 6 h and at the G2/M checkpoint at 12 h, respectively. HU-induced apoptosis is considered to be mediated by p53 in the fetal brain.

Arthoscopic diagnosis of partial scapholunate ligament tears as a cause of radial sided wrist pain in patients with inconclusive x-ray and MRI findings.

To clarify the pathology of radial-sided wrist pain with inconclusive X-ray and MRI findings, we performed arthroscopic examinations of 11 wrists in 10 patients. Physical examination and various image investigations could not identify the cause of the pain. Arthroscopy revealed partial to complete tears of the scapho-lunate interosseous ligament and synovitis and/or chondral bone defects at the scaphotrapezio-trapezoidal joint in all 11 wrists. Surgical procedures consisted of eight simple synovectomies, two ligament reconstructions and one percutaneous pinning. Pain relief was achieved in 10 wrists. One wrist which had a simple synovectomy did not recover, so underwent secondary scaphotrapezio-trapezoidal fusion. In conclusion, we found that various degrees of scapholunate interosseous ligament tear and scaphotrapezio-trapezoidal joint osteoarthritis were the main causes of radial-sided wrist pain with inconclusive X-ray and simple MRI findings.

Functional outcome and quality of life after traumatic total brachial plexus injury treated by nerve transfer or single/double free muscle transfers: a comparative study.

AIMS: Between 2002 and 2011, 81 patients with a traumatic total brachial plexus injury underwent reconstruction by double free muscle transfer (DFMT, 47 cases), single muscle transfer (SMT, 16 cases) or nerve transfers (NT, 18 cases). METHODS: They were evaluated for functional outcome and quality of life (QoL) using the Disability of Arm, Shoulder and Hand questionnaire, both pre- and post-operatively. The three groups were compared and followed-up for at least 24 months. RESULTS: The mean shoulder abduction and flexion were comparable in all groups, but external rotation was significantly better in the DFMT group as were range and quantitative power of elbow flexion. Patients who had undergone DFMT had reasonable total active finger movement and hook grip strength. All groups showed improvement in function at a level greater than a minimum clinically important difference. The DFMT group showed the greatest improvement. DISCUSSION: Patients in the DFMT group had a better functional outcome and QoL recovery than those in the NT and SMT groups. TAKE HOME MESSAGE: Double free muscle transfer procedure is capable of restoring maximum function in patients of total brachial plexus palsy.