Optical development in the murine eye lens of accelerated senescence-prone SAMP8 and senescence-resistant SAMR1 strains.

The eye lens is responsible for focusing objects at various distances onto the retina and its refractive power is determined by its surface curvature as well as its internal gradient refractive index (GRIN). The lens continues to grow with age resulting in changes to the shape and to the GRIN profile. The present study aims to investigate how the ageing process may influence lens optical development. Murine lenses of accelerated senescence-prone strain (SAMP8) aged from 4 to 50 weeks; senescence-resistant strain (SAMR1) aged from 5 to 52 weeks as well as AKR strain (served as control) aged from 6 to 70 weeks were measured using the X-ray interferometer at the SPring-8 synchrotron Japan within three consecutive years from 2020 to 2022. Three dimensional distributions of the lens GRIN were reconstructed using the measured data and the lens shapes were determined using image segmentation in MatLab. Variations in the parameters describing the lens shape and the GRIN profile with age were compared amongst three mouse strains. With advancing age, both the lens anterior and posterior surface flattens and the lens sagittal thickness increase in all three mouse strains (Anterior radius of curvature increase at 0.008 mm/week, 0.007 mm/week and 0.002 mm/week while posterior radius of curvature increase at 0.002 mm/week, 0.007 mm/week and 0.003 mm/week respectively in AKR, SAMP8 and SAMR1 lenses). Compared with the AKR strain, the SAMP8 samples demonstrate a higher rate of increase in the posterior curvature radius (0.007 mm/week) and the thickness (0.015 mm/week), whilst the SAMR1 samples show slower increases in the anterior curvature radius (0.002 mm/week) and its thickness (0.013 mm/week). There are similar age-related trends in GRIN shape in the radial direction (in all three types of murine lenses nr2 and nr6 increase with age while nr4 decrease with age consistently) but not in the axial direction amongst three mouse strains (nz1 of AKR lens decrease while of SAMP8 and SAMR1 increase with age; nz2 of all three models increase with age; nz3 of AKR lens increase while of SAMP8 and SAMR1 decrease with age). The ageing process can influence the speed of lens shape change and affect the GRIN profile mainly in the axial direction, contributing to an accelerated decline rate of the optical power in the senescence-prone strain (3.5 D/week compared to 2.3 D/week in the AKR control model) but a retardatory decrease in the senescence-resistant strain (2.1 D/week compared to the 2.3D/week in the AKR control model).

Effects of Ndufs4 Deletion on Hearing after Various Acoustic Exposures.

Mitochondrial dysfunction can cause cochlear dysfunction and accelerate noise-induced hearing loss (NIHL). NADH dehydrogenase (ubiquinone) Fe-S protein 4 (Ndufs4) is one of the subunits of mitochondrial complex I and has a role in the assembly and stabilization of complex I. However, the involvement of Ndufs4 in the pathogenesis of NIHL has not been reported. The aim of this study was to evaluate whether Ndufs4 deletion causes vulnerability to noise exposures. The wild-type (WT) and Ndufs4 knockout (KO) mice with C57BL/6J genetic background were used. Cochlear histology and hearing thresholds were assessed after noise exposure at 100 or 86 dB sound pressure level (SPL). Immunostaining showed the widespread expression of Ndufs4 in the cochlea. After noise exposure at 100 dB SPL, auditory brainstem response (ABR) threshold shifts at 4 kHz in Ndufs4 KO mice were significantly higher than that in WT mice. After noise exposure at 86 dB SPL, ABR threshold shifts, wave 1 amplitudes, and the number of synapses in the inner hair cells were not significantly different. RNA sequencing revealed the decreased expression of energy generation-related genes inNdufs4 KO mice. Ndufs4 deficiency accelerates permanent low-frequency threshold shifts after moderate noise exposure.

[Development of autoimmune hemolytic anemia after BNT162b2 mRNA COVID-19 vaccination].

A 75-year-old woman with a history of postoperative chemotherapy for lung adenocarcinoma and a history of Helicobacter pylori eradication for idiopathic thrombocytopenic purpura (ITP) was admitted to the department of hematology and oncology for the treatment of anemia 2 weeks after BNT162b2 mRNA COVID-19 vaccination. Her blood examination revealed direct and indirect Coombs test-positive hemolytic anemia and elevation of serum LDH and indirect bilirubin levels. No obvious trigger other than BNT162b2 mRNA COVID-19 vaccination was found. She was diagnosed with autoimmune hemolytic anemia (AIHA), and oral prednisolone therapy was administered. The anemia improved soon after the administration of prednisolone. Although vaccination is considered to be very important for suppressing the spread of COVID-19, there have been reports of increasing risk of ITP development and deterioration caused by BNT162b2 mRNA COVID-19 vaccination. Because the number of vaccinated people is increasing rapidly, hematologists must be vigilant to the development of AIHA after BNT162b2 mRNA COVID-19 vaccination although case reports of this phenomenon have been very rare thus far.

Effects of intravenous injection of indocyanine green on the oxygen reserve index (ORi™).

PURPOSE: The oxygen reserve index (ORi™) is a parameter used for the noninvasive evaluation of arterial partial pressure of oxygen (PaO2), specifically in the 100-200 mmHg range. We aimed to report on the impact of indocyanine green (ICG) on the ORi™. METHODS: In this study, we retrospectively examined patients who underwent neurosurgery between April and July 2019 and assessed the impact of ICG on ORi™. We excluded patients who did not use ICG or who were not examined for ORi™. The dose and timing of ICG administration were determined by a neurosurgeon. The changes in ORi™ were measured for up to 30 min. RESULTS: We analyzed ten patients and found that the ORi™ increased to 1.00 in all of them. The median time for ORi ™ to rise to 1.00 after ICG administration was 2 min (range 1-4). After rising to 1.00, ORi ™ decreased and took 27 min to return to the pre-dose value. CONCLUSION: It is important to consider the initial rapid increase and subsequent slow decrease in ORi™ when using ICG during surgery.

[Classic Hodgkin lymphoma developing early after treatment of follicular lymphoma].

There are few reports of a patient presenting with combined follicular lymphoma (FL) and classical Hodgkin lymphoma (cHL). A 37-year-old Japanese man was diagnosed with FL with generalized lymphadenopathy and treated with R-CHOP. Four months later, he presented with fever, elevated lactic acid dehydrogenase (LDH), and pancytopenia. Consequently, he was diagnosed with cHL in the bone marrow. Identical clonality of FL and cHL tumor cells suggested identical immunoglobulin heavy chain gene rearrangements. He was treated with salvage chemotherapy and high-dose chemotherapy with autologous hematopoietic stem cell transformation (HDT-ASCT), which has led to complete remission and no recurrence for more than two years after transplantation. Our case suggests that HDT-ASCT may be an effective treatment for this rare clinical condition.

NEUROD1-deficient diabetes (MODY6): Identification of the first cases in Japanese and the clinical features.

AIMS: Only a few families with neuronal differentiation 1 (NEUROD1)-deficient diabetes, currently designated as maturity-onset diabetes of the young 6 (MODY6), have been reported, but mostly in Caucasian, and no mutation has been identified by family-based screening in Japanese. Accordingly, the phenotypic details of the disease remain to be elucidated. METHODS: We examined a total of 275 subjects having diabetes suspected to be MODY who were negative for mutations in MODY1-5 referred from 155 medical institutions throughout Japan. So as not to miss low penetrant cases, we examined non-obese Japanese patients with early-onset diabetes regardless of the presence of family history by direct sequencing of all exons and flanking regions of NEUROD1 . Large genomic rearrangements also were examined. RESULTS: Four patients with 3 frameshift mutations and 1 missense mutation, all of which were heterozygous and 3 of which were novel, were identified. Diabetic ketosis was found occasionally in these patients even under conditions of chronic hyperglycemia, for unknown reasons. Although the capacity of early-phase insulin secretion was low in these patients, the insulin secretory capacity was relatively preserved compared to that in hepatocyte nuclear factor (HNF)1A- and HNF1B-MODY. One of the patients and 2 of their diabetic mothers were found to have some mental or neuronal abnormality. CONCLUSIONS: This is the first report of NEUROD1 mutations in Japanese, who have a genetic background of intrinsically lower capacity of insulin secretion. NEUROD1-deficient diabetes appears to be low penetrant, and may occur in concert with other genetic factors.

Resveratrol derivative-rich melinjo (Gnetum gnemon L.) seed extract improves obesity and survival of C57BL/6 mice fed a high-fat diet.

Melinjo (Gnetum gnemon L.) seed extracts (MSEs) are rich in resveratrol dimers (gnemonoside A, C, D, gnetin C), trans-resveratrol, and other resveratrol derivatives. trans-Resveratrol is a widely studied caloric restriction mimetic. In mice fed a high-fat diet (HFD), trans-resveratrol protects against obesity, type 2 diabetes, and premature death. Here, treatment of HFD-fed mice with 2.0% MSE significantly reduced body weight gain (p < 0.001), blood insulin (p < 0.01), and HOMA-IR (p < 0.05) after 8 weeks compared with untreated HFD-fed mice. Additionally, 0.2% MSE treatment of HFD-fed mice significantly improved physiological activity (p < 0.05) at 18 months of age and reduced risk of death due to HFD by 25% (hazard ratio = 0.75, p = 0.036). These data show that MSE can improve several aspects of metabolic syndrome and survival in mice and may have health benefits as a dietary supplement.

Urinary retention occurring one week after spinal anesthesia: a case of Elsberg syndrome.

PURPOSE: We describe a case of urinary retention caused by viral sacral myeloradiculitis (Elsberg syndrome) that occurred one week after spinal anesthesia. The differential diagnosis of urinary retention after spinal anesthesia is discussed. CLINICAL FEATURES: A 76-yr-old male patient presented for operative removal of a right testicular hydrocele under spinal anesthesia. Anesthesia and surgery were uneventful, and he was discharged on the fifth postoperative day. Two days after discharge, he developed intermittent anal pain and voiding difficulty and was readmitted to hospital on the tenth postoperative day. He subsequently developed urinary retention, incontinence of feces, and difficulty in defecation. Magnetic resonance imaging showed no epidural hematoma, abscess, or other lesions in the spinal column, cauda equina, or spinal cord. Neurological examination showed dysesthesia in the perineal region and loss of the anal reflex and bulbocavernosus response, which indicated sacral (S4-5) radiculopathy or a lesion of the conus of the spinal cord. A cerebrospinal analysis showed slight elevation of protein without pleocytosis. After neurologic consultation, herpetic sacral myeloradiculitis was suspected and intravenous acyclovir was administered along with large doses of methylprednisolone and immunoglobulin. The symptoms gradually resolved, and the difficulty in voiding resolved 19 days after initiation of the treatment. The patient was discharged 23 days after the start of the treatment without any other complications. CONCLUSION: This case suggests that Elsberg syndrome is important in the differential diagnosis of urinary retention after spinal anesthesia and should be discriminated from other anesthesia-related complications.

Integrating an infectious disease programme into the primary health care service: a retrospective analysis of Chagas disease community-based surveillance in Honduras.

BACKGROUND: Integration of disease-specific programmes into the primary health care (PHC) service has been attempted mostly in clinically oriented disease control such as HIV/AIDS and tuberculosis but rarely in vector control. Chagas disease is controlled principally by interventions against the triatomine vector. In Honduras, after successful reduction of household infestation by vertical approach, the Ministry of Health implemented community-based vector surveillance at the PHC services (health centres) to prevent the resurgence of infection. This paper retrospectively analyses the effects and process of integrating a Chagas disease vector surveillance system into health centres. METHODS: We evaluated the effects of integration at six pilot sites in western Honduras during 2008-2011 on; surveillance performance; knowledge, attitude and practice in schoolchildren; reports of triatomine bug infestation and institutional response; and seroprevalence among children under 15 years of age. The process of integration of the surveillance system was analysed using the PRECEDE-PROCEED model for health programme planning. The model was employed to systematically determine influential and interactive factors which facilitated the integration process at different levels of the Ministry of Health and the community. RESULTS: Overall surveillance performance improved from 46 to 84 on a 100 point-scale. Schoolchildren's attitude (risk awareness) score significantly increased from 77 to 83 points. Seroprevalence declined from 3.4% to 0.4%. Health centres responded to the community bug reports by insecticide spraying. As key factors, the health centres had potential management capacity and influence over the inhabitants' behaviours and living environment directly and through community health volunteers. The National Chagas Programme played an essential role in facilitating changes with adequate distribution of responsibilities, participatory modelling, training and, evaluation and advocacy. CONCLUSIONS: We found that Chagas disease vector surveillance can be integrated into the PHC service. Health centres demonstrated capacity to manage vector surveillance and improve performance, children's awareness, vector report-response and seroprevalence, once tasks were simplified to be performed by trained non-specialists and distributed among the stakeholders. Health systems integration requires health workers to perform beyond their usual responsibilities and acquire management skills. Integration of vector control is feasible and can contribute to strengthening the preventive capacity of the PHC service.

Clear cell carcinoma of the base of the tongue: case report and literature review.

OBJECTIVE: Clear cell carcinoma (CCC) is a rare, low-grade malignant neoplasm of minor salivary glands. Clear cell carcinoma is composed of monomorphic clear cells that contain glycogen within a hyalinized stroma. The microscopic diagnosis can be challenging, and the treatment strategy has not been established. METHODS: We report a case of a 56-year-old woman with CCC in the base of the tongue. A literature review, including 22 published cases and our case, was performed to clarify the clinical characteristics of CCC in the base of the tongue. RESULTS: The exophytic tumor showed no infiltration to the neighboring tissues. She underwent a local excision en bloc transorally and is free of the disease 15 months after surgery. In our review of 23 cases of CCC in the base of the tongue, 21 cases received surgical excision for the purpose of the primary treatment modality. The fact that the distinctive features of restricted site-related symptoms and the rare presentation of pain emerged was similar to previously reported cases of CCC. A relatively good prognosis was still indicated. CONCLUSION: We reveal the features of the unusual occurrence of CCC in the base of the tongue and consider the appropriate surgical approach for primary treatment.

Biomechanical Study of the Digital Flexor Tendon Sliding Lengthening Technique.

PURPOSE: To compare the mechanical properties of sliding lengthening (SL) and Z-lengthening (ZL) for flexor tendon elongation used for conditions such as Volkmann contracture, cerebral palsy, and poststroke spasticity. METHODS: We harvested 56 flexor tendons, including flexor pollicis longus tendons, flexor digitorum superficialis tendons (zones II to IV), and flexor digitorum profundus tendons (zones II to V) from 24 upper limbs of 12 fresh cadavers. Each tendon was harvested together with its homonymous tendon from the opposite side of the cadaver and paired. We used 28 pairs of tendons and divided them randomly into 4 groups depending on the lengthening distance (20 or 30 mm) and type of stitching (single or double mattress sutures). Then we divided each pair into either the SL or ZL group. Each group was composed of 7 specimens. The same surgeon lengthened all tendons and stitched them with 2-0 polyester sutures. We tested biomechanical tensile strength immediately after completing lengthening and suturing in each group. RESULTS: Ultimate tensile strengths were: 23 N for the SL 20-mm lengthening and single mattress suture and 7 N for the ZL; 25 N for the SL 20-mm lengthening and double mattress suture and 10 N for the ZL; 15 N for the SL 30-mm lengthening and single mattress suture and 8 N for the ZL; and 18 N for the SL 30-mm lengthening and double mattress suture and 10 N for the ZL. CONCLUSIONS: The SL technique may be a good alternative to the ZL technique because it provides higher ultimate tensile strength. CLINICAL RELEVANCE: Because of its higher ultimate tensile strength, the SL technique may allow for earlier rehabilitation and reduced risk of postoperative complications.

Certifying achievement in the control of Chagas disease native vectors: what is a viable scenario?

As an evaluation scheme, we propose certifying for "control", as alternative to "interruption", of Chagas disease transmission by native vectors, to project a more achievable and measurable goal and sharing good practices through an "open online platform" rather than "formal certification" to make the key knowledge more accumulable and accessible.

[Loss of anesthesia records during network failure of anesthesia management information system: a case of malfunction of backup system].

We report a case of an accidental loss of anesthesia records through network failure of an anesthesia information management system (AIMS). The backup data were not kept in the anesthesia workstations or the server during the failure. Accordingly, anesthesia records of five patients were lost for one hour. Our AIMS has a network redundancy where the server keeps anesthesia monitoring data via two pathways: one via the monitoring server to the AIMS server and the other via anesthesia workstation to the server. Despite the redundant pathways, transient power failures of network switches caused interruptions in both pathways. Our case indicates that, to improve the robustness of the AIMS as electronic medical records, every network apparatus of AIMS, should be supplied with an uninterrupted power supply. Furthermore, each anesthesia workstation should function independently as an anesthesia record keeping client when network failure occurs.

[External auditory canal cholesteatoma with chronic renal failure or hemodialysis].

BACKGROUND: External auditory canal cholesteatoma (EACC) is a rare otologic disease, characterized by focal osteonecrosis, sequestration and overlying epithelial loss of the bony external auditory canal (EAC). The etiology and pathogenesis of EACC remain controversial. There are only 2 reports on the association between EACC and chronic renal failure (CRF)/hemodialysis (HD). METHOD & RESULT: (1) This study reviewed seven EACC cases with CRF. The mean age was 68.4 years (range: 56 -81 years), and the male-female ratio was 5:2. There were 12 ears with EACC (5 cases were bilateral and 2 cases were unilateral). The EACCs were found in the inferior or posterior inferior part of the EAC in 11 ears. The number of the ears in stage III or IV was 6. Five cases were on HD. (2) Seventy-six cases with CRF on HD were examined for EACC, and 2 out of those 70 cases were diagnosed as having EACC. (3) A comparative study of the 7 EACC cases on HD and 68 non-EACC cases on HD revealed no significant differences in the sex, age, period on CRF/HD, complications (diabetes mellitus or skin disease), smoking, ear cleaning and the use of an earphone or a hearing aid. CONCLUSION & DISCUSSION: Six out of all 9 EACC cases with CRF developed bilaterally, and in the inferior or posterior inferior part of the EAC, which implies a common pathological condition that contributes to the development of EACC. The mean age of 9 patients with EACC was relatively older (66.7 years), therefore age-related changes in the EAC are suspected in the cases with CRF on HD. The patients with CRF on HD have a high incidence of EACC. This strongly suggests the association between EACC and CRF/HD, but the mechanism of this pathogenesis has not been revealed.

Thermoelastic wave generation and its longitudinal wave propagation measurement by a microscopic optical interferometer.

Laser ultrasonics is a noncontact measurement method that uses a laser-induced elastic wave source in combination with an optical surface displacement-tracking system. This study compared the performances of two optical interferometers with different characteristics when applied to measurement of pulsed thermoelastic waves. The surface displacement-tracking system was designed to measure the center of the microscopic view. A pulsed laser beam irradiated a black ink layer to generate the thermoelastic waves. The out-of-plane displacement on the axially opposite side was then measured using either a Michelson interferometer or a Sagnac interferometer. The objective lens of the system was of a type commonly used in biological observations. The Michelson interferometer estimated a maximum displacement of 0.43 nm and a maximum sound pressure of 24.7 kPa. The signal-to-noise ratios from 16 averages were 14.9 dB (Michelson interferometer) and 19.2 dB (Sagnac interferometer). Furthermore, this paper compares the performance of the numerically estimated Sagnac interferometer outputs calculated from the measured Michelson interferometer outputs with the experimentally obtained Sagnac interferometer outputs. The numerically estimated Sagnac interferometer's output was shown to be identical to the experimentally acquired output. The Michelson interferometer requires a higher average operating frequency (i.e., it needs a longer data acquisition time), although this interferometer does offer superior displacement output linearity. This property enables calculation of the sound pressure from the displacement amplitude. These findings indicated that combination of the measurement points of the Sagnac interferometer with those of the sparsely distributed Michelson interferometer reduced the measurement time when compared with a single use of the Michelson interferometer while also maintaining the data acquisition quality.

Comparative analysis of ventricular stiffness across species.

Investigating ventricular diastolic properties is crucial for understanding the physiological cardiac functions in organisms and unraveling the pathological mechanisms of cardiovascular disorders. Ventricular stiffness, a fundamental parameter that defines ventricular diastolic functions in chordates, is typically analyzed using the end-diastolic pressure-volume relationship (EDPVR). However, comparing ventricular stiffness accurately across chambers of varying maximum volume capacities has been a long-standing challenge. As one of the solutions to this problem, we propose calculating a relative ventricular stiffness index by applying an exponential approximation formula to the EDPVR plot data of the relationship between ventricular pressure and values of normalized ventricular volume by the ventricular weight. This article reviews the potential, utility, and limitations of using normalized EDPVR analysis in recent studies. Herein, we measured and ranked ventricular stiffness in differently sized and shaped chambers using ex vivo ventricular pressure-volume analysis data from four animals: Wistar rats, red-eared slider turtles, masu salmon, and cherry salmon. Furthermore, we have discussed the mechanical effects of intracellular and extracellular viscoelastic components, Titin (Connectin) filaments, collagens, physiological sarcomere length, and other factors that govern ventricular stiffness. Our review provides insights into the comparison of ventricular stiffness in different-sized ventricles between heterologous and homologous species, including non-model organisms.

Remimazolam-based total intravenous anesthesia in a patient with a confirmed diagnosis of malignant hyperthermia: a case report.

BACKGROUND: Malignant hyperthermia (MH) is a rare, life-threatening disorder of calcium homeostasis in skeletal muscle cells that is triggered by volatile anesthetics and succinylcholine, leading to a hypermetabolic reaction. The pathogenic ryanodine receptor 1 (RYR1) gene variant is critical. Patients susceptible to MH should avoid triggering agents, and total intravenous anesthesia (TIVA) is preferred. Remimazolam is safe in patients with suspected MH. CASE PRESENTATION: We present the first case of remimazolam treatment in a genetically confirmed patient with MH without MH development. A 72-year-old man with a family history of MH underwent remimazolam-based TIVA. After informed consent was obtained, a muscle biopsy and genetic testing were performed. Intraoperatively and postoperatively, the patient exhibited no signs of MH. An enhanced function of the RYR1 channel into releasing calcium was indicated, and the genetic testing revealed a pathogenic variant of RYR1. CONCLUSIONS: Remimazolam-based TIVA is safe in patients confirming the diagnosis of MH.

Loss of connectin novex-3 leads to heart dysfunction associated with impaired cardiomyocyte proliferation and abnormal nuclear mechanics.

Connectin (also known as titin) is a giant striated muscle protein that functions as a molecular spring by providing elasticity to the sarcomere. Novex-3 is a short splice variant of connectin whose physiological function remains unknown. We have recently demonstrated using in vitro analyses that in addition to sarcomere expression, novex-3 was also expressed in cardiomyocyte nuclei exclusively during fetal life, where it provides elasticity/compliance to cardiomyocyte nuclei and promotes cardiomyocyte proliferation in the fetus, suggesting a non-sarcomeric function. Here, we analyzed novex-3 knockout mice to assess the involvement of this function in cardiac pathophysiology in vivo. Deficiency of novex-3 compromised fetal cardiomyocyte proliferation and induced the enlargement of individual cardiomyocytes in neonates. In adults, novex-3 deficiency resulted in chamber dilation and systolic dysfunction, associated with Ca2+ dysregulation, resulting in a reduced life span. Mechanistic analyses revealed a possible association between impaired proliferation and abnormal nuclear mechanics, including stiffer nuclei positioned peripherally with stabilized circumnuclear microtubules in knockout cardiomyocytes. Although the underlying causal relationships were not fully elucidated, these data show that novex-3 has a vital non-sarcomeric function in cardiac pathophysiology and serves as an early contributor to cardiomyocyte proliferation.

A case of autoimmune encephalitis in a patient with a solitary intracranial plasmacytoma.

A 65-year-old woman presented with fever and abnormal behavior. Magnetic resonance imaging showed swelling of the left medial temporal lobe and an intracranial extra-axial occipital tumor. While her neurological symptoms improved after the administration of corticosteroid therapy under the suspicion of autoimmune encephalitis, the occipital tumor unexpectedly shrank, and the diagnosis of a solitary plasmacytoma was confirmed by biopsy. Additional examinations revealed elevated anti-glutamate receptor antibodies in the cerebrospinal fluid. The patient was diagnosed with autoimmune encephalitis concurrent with an intracranial solitary plasmacytoma. Central nervous system involvement can be considered a neurological complication in patients with a solitary plasmacytoma.