Localized Expression of Olfactory Receptor Genes in the Olfactory Organ of Common Minke Whales.

Baleen whales (Mysticeti) possess the necessary anatomical structures and genetic elements for olfaction. Nevertheless, the olfactory receptor gene (OR) repertoire has undergone substantial degeneration in the cetacean lineage following the divergence of the Artiodactyla and Cetacea. The functionality of highly degenerated mysticete ORs within their olfactory epithelium remains unknown. In this study, we extracted total RNA from the nasal mucosae of common minke whales (Balaenoptera acutorostrata) to investigate ORs' localized expression. All three sections of the mucosae examined in the nasal chamber displayed comparable histological structure. However, the posterior portion of the frontoturbinal region exhibited notably high OR expression. Neither the olfactory bulb nor the external skin exhibited the expression of these genes. Although this species possesses four intact non-class-2 ORs, all the ORs expressed in the nasal mucosae belong to class-2, implying the loss of aversion to specific odorants. These anatomical and genomic analyses suggest that ORs are still responsible for olfaction within the nasal region of baleen whales, enabling them to detect desirable scents such as prey and potential mating partners.

Morphology of the asymptomatic Αchilles tendon: Measurement of tendon length and shape using magnetic resonance imaging, and investigation of related factors.

BACKGROUND: One of the severe complications of Achilles tendon (AT) rupture is muscle weakness due to tendon lengthening. It is very important to prevent tendon lengthening during treatment; however, data on the length, thickness, and width of normal ATs are scarce. Furthermore, no studies have investigated the factors related to the AT length and shape. We aimed to determine the normal AT length and shape and to investigate any correlating factors. METHODS: We measured the AT length, thickness, and width of 100 asymptomatic patients using magnetic resonance imaging. We also investigated the correlation between the AT length, thickness, and width and factors including age, sex, height, body weight, body mass index, history of sports activities, and the area of Kager's fat pad. RESULTS: The mean AT length was 42.1 ± 12.9 mm. The AT length in 73% of the patients was within the range of 30-55 mm. Individual differences in the tendon length were large, but there was no correlation between the tendon length and patient height (P = 0.505). There was a strong correlation between the AT length and area of Kager's fat pad on magnetic resonance imaging (r = 0.734, P < 0.001). Furthermore, the correlation coefficient between the area of Kager's fat pad on magnetic resonance imaging and the area of Kager's triangle on radiography was extremely high (r = 0.851, P < 0.001). CONCLUSIONS: The AT length can be predicted based on the area of Kager's triangle of the unaffected ankle on radiography. If the AT length is > 55 mm or longer than the length measured directly or calculated from the estimated area of Kager's triangle, tendon lengthening should be suspected. Our findings could provide an important indicator for the evaluation of AT lengthening not only in daily clinical situations but also in clinical studies.

Plantar pressure distribution in hallux valgus feet after a first metatarsal proximal crescentic osteotomy with a lesser metatarsal proximal shortening osteotomy.

BACKGROUND: Plantar pressure distribution after the first metatarsal proximal crescentic osteotomy (FMPCO) with lesser metatarsal proximal shortening osteotomy (LMPSO) for hallux valgus with metatarsalgia has not been previously described. METHODS: The pre- (Pre) and postoperative (Post) groups comprised of 18 patients who underwent unilateral FMPCO with LMPSO; fifteen healthy volunteers constituted the control (C) group. For each of the 10 regions, peak pressure (Peak-P), maximum force (Max-F), contact time (Con-T), contact area (Con-A), and force-time integral (FTI) were measured. RESULTS: The mean Peak-P of the second metatarsal head was significantly lower in the Post group than the Pre group. The mean Peak-P, Max-F, Con-T, and FTI were not significantly different between the Post and C groups. The mean Con-A was significantly lower in the Post group than the C group. CONCLUSION: FMPCO with LMPSO may improve the plantar pressure of the central forefoot comparable to healthy subjects.

Postural stability impairment in patients with bilateral hallux valgus: A case-control study using a stabilometer.

BACKGROUND: Hallux valgus (HV) is an important risk factor for falls (in older people); however, the detailed relationship is less understood. We aimed to evaluate postural stability in bilateral HV patients. METHODS: Two groups of 20 female patients-an HV group and a C (i.e., non-HV) group-participated in this study. Evaluations were made using the Timed Up and Go (TUG) test, the Berg Balance Scale (BBS), the Falls Efficacy Scale (FES), track length (LNG), velocity (VEL), enveloped area (ENV), and root mean square area (RMS). RESULTS: TUG and FES scores were significantly higher and BBS scores were lower in the HV group than in the C group. LNG was significantly longer, VEL was higher, and ENV and RMS were wider in the HV group than in the C group. CONCLUSIONS: The HV group exhibited impaired walking mobility, balance, and postural stability.

Fast and robust reconstruction algorithm for fluorescence diffuse optical tomography assuming a cuboid target.

A fast algorithm for fluorescence diffuse optical tomography is proposed. The algorithm is robust against the choice of initial guesses. We estimate the position of a fluorescent target by assuming a cuboid (rectangular parallelepiped) for the fluorophore target. The proposed numerical algorithm is verified by a numerical experiment and an experiment with a meat phantom. The target position is reconstructed with a cuboid from measurements in the time domain. Moreover, the long-time behavior of the emission light is investigated making use of the analytical solution to the diffusion equation.

Magnetic resonance imaging of bone marrow for TAFRO syndrome.

We report two cases of TAFRO syndrome, which is characterized by thrombocytopenia, anasarca, fever, renal insufficiency, and organomegaly. Magnetic resonance imaging (MRI) of the spine showed a dark medullary pattern in the bone marrow on the T1- and T2-weighted images of both patients. One patient showed complete resolution after treatment. Serial MRIs of the improved patient revealed a transition to a normal marrow pattern on both images, which might represent resolution of the disease.

Distribution and Local Movement of Humpback Whales in Okinawan Waters Depend on Sex and Reproductive Status.

The distribution and local movement patterns of humpback whales in waters off the west coast of Okinawa Island, southwest Japan, were investigated using line transect and photo-identification methodologies. Line transect surveys were conducted from 2011 to 2014 and photo-identification survey from 2006 to 2012. During the surveys, humpback whales aggregated in the areas around Ie and Kerama Islands, and tended to travel along the inshore coast of Okinawa Island when they move locally between those two sites. A total of 496 humpback whales of the known sex were photo-identified (322 males, 75 females and 99 females with a calf). Of these, 24.8% were confirmed moving locally between the sites of Ie and Kerama Islands within the same season. Frequency rates of the local movement for males, females and females with a calf were 41.9, 25.0, and 15.1%, respectively; the frequency of local movement for males was significantly higher than that for females and females with a calf. These results indicate that male humpback whales tend to move more actively between the local breeding sites as compared to females and females with a calf. We speculate that the males search for more opportunities to mate, whereas females with a calf tend to remain in the same areas to nurse their calves. These findings extend our knowledge of the habitat use and reproductive ecology of humpback whales in Okinawan waters, which remain poorly understood.

A case of acute liver failure caused by Budd-Chiari syndrome salvaged by brain-dead donor liver transplantation.

A 24-year-old man was admitted to our hospital with abdominal distension. He was found to have acute liver failure and diagnosed with Budd-Chiari syndrome based on angiography and liver biopsy. Liver transplantation was deemed necessary when angiography showed extensive thrombotic occlusion of the hepatic veins and liver biopsy revealed submassive hepatic necrosis. The patient was found to have the JAK2V617F mutation, indicating a myeloproliferative neoplasm as the background disease. He developed hepatic encephalopathy but remained conscious on on-line hemodiafiltration. Brain-dead donor liver transplantation was performed on hospital day 30. Since then, the patient has remained well.

Hemophagocytic Lymphohistiocytosis and Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis Possibly Caused by Enterococcus faecalis Infective Endocarditis.

Infection can induce hemophagocytic lymphohistiocytosis (HLH) and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We herein report a 52-year-old man who had HLH and AAV simultaneously, possibly caused by Enterococcus faecalis infective endocarditis. The HLH diagnosis was based on the HLH-2004 criteria. AAV was diagnosed based on a positive result for proteinase-3 ANCA and necrotizing vasculitis of the small vessels on a skin biopsy. He eventually died and was sent for autopsy after combination treatment of valve replacement, antibiotics, and immunosuppressants, including corticosteroids. This case involved a challenging diagnosis and treatment of HLH with various complications in an adult.

Acute heart failure due to left common iliac arteriovenous fistula: A case of VEXAS syndrome.

We describe the case of a 78-year-old man presenting with multiple oedematous erythemas, fever, and arthralgia who subsequently developed neutrophil infiltration into the cartilage of the bilateral auricularis, consistent with relapsing polychondritis. A skin biopsy of the erythema on his right arm showed dense neutrophilic infiltration into the dermis, while a bone marrow aspirate revealed myelodysplastic syndromes with characteristic vacuoles in myeloid precursor cells. Although the patient achieved remission with high-dose oral prednisolone, the inflammatory symptoms relapsed, and he was resistant to colchicine and cyclosporine. The patient spontaneously developed left leg oedema and high-output cardiac failure caused by an arteriovenous fistula with a common iliac artery aneurysm. We successfully performed a two-stage surgery using internal iliac artery coil embolisation and endovascular aortic repair of the iliac aneurysm. We assumed the patient was suffering from large-vessel vasculitis such as giant cell arteritis or Takayasu's arteritis. We treated him with tocilizumab in addition to prednisolone, and the febrile events and elevated C-reactive protein levels improved. One year later, sequencing of ubiquitylation-initiating E1 enzyme using peripheral blood leucocytes revealed somatic variants (c.121A>C p.Met41Leu), confirming the diagnosis of vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. This case suggests that arteriovenous fistula could be a complication of VEXAS syndrome with large-vessel vasculitis, and adequate surgical intervention and prompt diagnosis are essential for rescue. Although arteriovenous fistula is a rare complication of VEXAS syndrome, physicians should be aware of this complication to ensure prompt diagnosis and timely surgical intervention.

Effect of charcoal hemoperfusion for removal of plasma methotrexate in a patient with acute renal failure.

Strategies effective for accelerating methotrexate removal in delayed methotrexate excretion have not been universally accepted. The authors report a case of a 12-year-old girl with osteosarcoma who developed acute renal failure immediately after the first administration of high-dose methotrexate. Plasma methotrexate was effectively removed with repeated charcoal hemoperfusion in addition to plasma exchange and leucovorin rescue. Charcoal hemoperfusion was most effective for reducing plasma methotrexate with approximately 50% of methotrexate being reduced during each of the procedures. No rebound increase in MTX levels was observed. The patient received further therapy with other cancer drugs and has been well for 3.5 years.

Acute Compartment Syndrome of the Forearm Secondary to Hematoma after Playing Golf.

Acute compartment syndrome of the forearm secondary to hematoma without direct trauma has been reported rarely. We report a case of acute compartment syndrome of the forearm following a hematoma after playing golf. A 55-year-old man felt pain in his left forearm while playing golf that gradually worsened. He could not continue to play and visited the emergency department of our hospital. The radial side of his left forearm was markedly swollen on presentation, and he suffered severe pain that worsened with ulnar flexion of the wrist; no paralysis or hypesthesia was observed. A hematoma in the brachioradialis was seen on magnetic resonance imaging, and radial compartment pressure was 120 mmHg. A diagnosis of acute compartment syndrome was made, and urgent fasciotomy was performed. The patient recovered with no dysfunction of the arm.

[Case report of acute encephalopathy caused by enterohemorrhagic Escherichia coli infection in a 24-year-old woman].

Hemolytic uremic syndrome (HUS) and acute encephalopathy caused by enterohemorrhagic Escherichia coli infection occur commonly in children, whereas adult-onset disease is rare. Here we report the case of a 24-year-old woman who developed acute encephalopathy and recovered without sequelae. She initially developed abdominal pain and diarrhea. On day 6, O-157 Shiga toxin was detected in her stool and she developed HUS. On day 11, acute encephalopathy developed and she required artificial ventilation. She was treated with steroid pulse therapy and plasma exchange (PE) and then discharged on day 53 without any sequelae. Globotriaosylceramide, a Shiga toxin receptor, is more frequently present on the cellular membranes of women than on those of men. Therefore, it is conceivable that adult women are at a higher risk of developing acute encephalopathy than men. Steroid pulse therapy and PE may effectively treat acute encephalopathy by reducing inflammatory cytokine levels in the blood; therefore, these treatments should be proactively considered.

Novel mutations of the GLA gene in Japanese patients with Fabry disease and their functional characterization by active site specific chaperone.

Fabry disease is an X-linked recessive inborn metabolic disorder caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (EC 3.2.1.22). The causative mutations are diverse, include both large rearrangements and single-base substitutions, and are dispersed throughout the 7 exons of the alpha-galactosidase A gene (GLA). Mutation hotspots for Fabry disease do not exist. We examined 62 Fabry patients in Japan and found 24 GLA mutations, including 11 novel ones. A potential treatment reported for Fabry disease is active site specific chaperone (ASSC) therapy using 1-deoxygalactonojirimycin (DGJ), an inhibitor of alpha-galactosidase A, at subinhibitory concentrations. We transfected COS-7 cells with the 24 mutant GLAs and analyzed the alpha-galactosidase A activities. We then treated the transfected COS-7 cells with DGJ and analyzed its effect on the mutant enzyme activities. The activity of 11 missense mutants increased significantly with DGJ. Although ASSC therapy is useful only for misfolding mutants and therefore not applicable to all cases, it may be useful for treating many Japanese patients with Fabry disease.

Naked plasmid DNA-based alpha-galactosidase A gene transfer partially reduces systemic accumulation of globotriaosylceramide in Fabry mice.

Fabry disease is an X-linked recessive inborn metabolic disorder in which a deficiency in lysosomal enzyme alpha-galactosidase A (Gal A) causes the systemic accumulation of globotriaosylceramide (Gb3). Although many investigators have attempted to treat alpha-Gal A knock-out mice (Fabry mice) with gene therapy, no report has demonstrated therapeutic effects by the retrograde renal vein injection of naked DNA. We recently developed a naked plasmid vector-mediated kidney-targeted gene transfer technique. A solution containing naked plasmid DNA encoding human alpha-Gal A (pKSCX-alpha-Gal A) was rapidly injected into the left kidney of Fabry mice (pKSCX-alpha-Gal A mice). pKSCX was used for mock transfections (pKSCX mice). We confirmed that vector-derived human alpha-Gal A mRNA was present in the left kidney but not in other tissues, by reverse transcriptase polymerase chain reaction. Compared with the pKSCX mice, the pKSCX-alpha-Gal A mice showed partial therapeutic effects: increased alpha-Gal A activity in the injected kidney and in the liver, heart, and plasma, and decreased Gb3 in the injected kidney, contralateral kidney, liver, heart, and spleen. Our results demonstrated that, although further studies are needed to improve the outcome, this method has promise as a potential treatment option for Fabry disease.

Numerical simulations of magnetic resonance elastography using finite element analysis with a linear heterogeneous viscoelastic model.

ABSTRACT: Magnetic resonance elastography (MRE) is a technique to identify the viscoelastic moduli of biological tissues by solving the inverse problem from the displacement field of viscoelastic wave propagation in a tissue measured by MRI. Because finite element analysis (FEA) of MRE evaluates not only the viscoelastic model for a tissue but also the efficiency of the inversion algorithm, we developed FEA for MRE using commercial software called ANSYS, the Zener model for displacement field of a wave inside tissue, and an inversion algorithm called the modified integral method. The profile of the simulated displacement field by FEA agrees well with the experimental data measured by MRE for gel phantoms. Similarly, the value of storage modulus (i.e., stiffness) recovered using the modified integral method with the simulation data is consistent with the value given in FEA. Furthermore, applying the suggested FEA to a human liver demonstrates the effectiveness of the present simulation scheme.

Sustained transgene expression in rat kidney with naked plasmid DNA and PCR-amplified DNA fragments.

Recently, we developed a kidney-targeted gene transfer technique, in which naked DNA was injected into the renal vein while the renal vein and artery were clamped. Kidney-targeted DNA transfer with only the renal vein clamped is an important modification that may permit less invasive catheter-based gene transfer in future clinical applications. The preparation of PCR-amplified DNA fragments is less time-consuming than that of naked plasmid DNA. We examined rat erythropoietin (Epo) plasmid, pCAGGS-Epo, or PCR-amplified DNA fragment, fCAGGS-Epo, transfer into the rat kidney with only the renal vein clamped. The Epo level peaked at week 3 and then was sustained for 24 weeks, which resulted in significant erythropoiesis. This modified technique, allowing long-term expression of both PCR-amplified DNA fragments and naked plasmid DNA, could potentially be used for catheter-based gene transfer in humans, and could help determine the physiological functions of putative genes.

Rat kidney-targeted naked plasmid DNA transfer by retrograde injection into the renal vein.

Kidney-targeted gene transfer is expected to revolutionize the treatment of renal diseases. Recently, we demonstrated that naked plasmid deoxyribonucleic acid (DNA) can be transferred into renal interstitial fibroblasts near the peritubular capillaries (PTCs) in normal rats, by retrograde injection into the renal vein with the renal vein and artery clamped. The PTC network is a main target of kidney transplant rejection and of progressive tubulointerstitial fibrosis, which typifies all progressive renal diseases. We retrogradely injected a lacZ expression plasmid in Ringer's solution into the renal vein of rats using a 24-gage catheter. We detected lacZ expression exclusively in the interstitial fibroblasts near the PTCs of the kidney by immunoelectron microscopy. Nephrotoxicity from the gene transfer was not apparent. We then used a rat erythropoietin (Epo) expression plasmid vector pCAGGS-Epo in a reporter assay. We obtained maximal Epo expression when the DNA solution was injected within 5 s in a volume of 1.0 mL. We detected transgene-derived Epo messenger ribonucleic acid by reverse transcriptase polymerase chain reaction only in the kidneys receiving pCAGGS-Epo. In this article, protocols for naked plasmid DNA transfer into rat kidney using this hydrodynamics-based transfection method and the immunoelectron microscopic technique to determine the lacZ gene transfer site are described in detail.