A synopsis of global frontiers in fertility preservation.

Since 2007, the Oncofertility Consortium Annual Conference has brought together a diverse network of individuals from a wide range of backgrounds and professional levels to disseminate emerging basic and clinical research findings in fertility preservation. This network also developed enduring educational materials to accelerate the pace and quality of field-wide scientific communication. Between 2007 and 2019, the Oncofertility Consortium Annual Conference was held as an in-person event in Chicago, IL. The conference attracted approximately 250 attendees each year representing 20 countries around the world. In 2020, however, the COVID-19 pandemic disrupted this paradigm and precluded an in-person meeting. Nevertheless, there remained an undeniable demand for the oncofertility community to convene. To maintain the momentum of the field, the Oncofertility Consortium hosted a day-long virtual meeting on March 5, 2021, with the theme of "Oncofertility Around the Globe" to highlight the diversity of clinical care and translational research that is ongoing around the world in this discipline. This virtual meeting was hosted using the vFairs ® conference platform and allowed over 700 people to participate, many of whom were first-time conference attendees. The agenda featured concurrent sessions from presenters in six continents which provided attendees a complete overview of the field and furthered our mission to create a global community of oncofertility practice. This paper provides a synopsis of talks delivered at this event and highlights the new advances and frontiers in the fields of oncofertility and fertility preservation around the globe from clinical practice and patient-centered efforts to translational research.

Ageing and chronic disease-related changes in the morphometric characteristics of ovarian follicles in cynomolgus monkeys (Macaca fascicularis).

STUDY QUESTION: How is the localisation of ovarian follicles affected by ageing and chronic diseases? SUMMARY ANSWER: Ovarian follicles shift deeper towards the medulla, due to thickening of the tunica albuginea (TA), with ageing and some major common chronic diseases. WHAT IS KNOWN ALREADY: The ovary undergoes morphological and functional changes with ageing. The follicular pool follows these changes with alterations in the amount and distribution of residual follicles. Diseases causing a chronic inflammatory process are associated with morphological changes and impaired ovarian function. STUDY DESIGN, SIZE, DURATION: We conducted a cross-sectional study, examining 90 ovaries from 90 female monkeys. The samples were collected from April 2018 to March 2019 at Tsukuba Primate Research Center in National Institutes of Biomedical Innovation, Health and Nutrition, Japan. PARTICIPANTS/MATERIALS, SETTING, METHODS: Ovarian samples were obtained from cynomolgus monkeys that died from natural causes or were euthanised. Ovarian sections were stained with haematoxylin and eosin (H&E) for histological analyses. In ovarian sections from 64 female macaques aged 0-25 years, a total of 13 743 follicles at different developmental stages (primordial, intermediary, primary, early secondary and late secondary) were assessed to determine the depth of each follicle from the outer surface of the ovarian cortex to the far end of the follicle, by using a digital imaging software. TA thickness was measured as sum of basal membrane and tunica collagen layer for each ovary under H&E staining. To explore the possibility of age-related trends in ovarian morphometric characteristics, samples were divided into four different age groups (0-3 years (pre-menarche), 4-9 years, 10-14 years and 15-20 years). To evaluate the effect of common chronic diseases on ovarian morphometric characteristics, macaques with diabetes mellitus (DM) (n = 10), endometriosis (n = 8) or inflammatory bowel disease (IBD) (n = 8) were compared to age-matched controls without chronic diseases. MAIN RESULTS AND THE ROLE OF CHANCE: Ovarian morphometric analysis revealed that the relative location of follicles became deeper in all age groups according to development of follicles (P < 0.05). Total follicle distance from the ovarian surface was increased with ageing (P < 0.05). In a sub-analysis according to developmental stage, only primordial and intermediary follicles were localised deeper with increasing age (P < 0.05). TA thickness was also increased with ageing (P < 0.05). The localisation of the total number of follicles became deeper in ovaries from monkeys with DM, endometriosis or IBD as compared to the control group (P < 0.05). With DM, analysis of follicles distance at almost each developmental stage was significantly deeper compared to controls (P < 0.05) with the exception of early secondary follicles. With endometriosis, follicles at primary and early and late secondary stages were significantly deeper compared to controls (P < 0.05). Also with IBD, follicles at primary and early and late secondary follicles were significantly deeper compared to controls (P < 0.001). The TA was thicker with DM and endometriosis compared to controls (P < 0.05), but not with IBD (P = 0.16). LARGE SCALE DATA: NA. LIMITATIONS, REASONS FOR CAUTION: Two-dimensional histology was used to assess follicle localisation. The possibility of minimal variations between the measured distance to the actual distance in a spherical structure cannot be excluded. Additionally, the severity of disease was not assessed. WIDER IMPLICATIONS OF THE FINDINGS: This study is the first step towards enhancing our understanding of how ageing and chronic diseases affect the relative localisation of dormant and developing follicles. These observations, combined with possible future human studies, may have managerial implications in the field of fertility preservation and other conditions involving ovarian tissue cryopreservation. STUDY FUNDING/COMPETING INTEREST(S): The present work was supported by the Grant-in-Aid for Scientific Research B (19H03801) (to K.K.), Challenging Exploratory Research (18K19624), Japan Agency for Medical Research and Development, Mochida Memorial Foundation for Medical and Pharmaceutical Research, Takeda Science Foundation and Naito Foundation (to K.K.). All authors have no conflicts of interest directly relevant to the content of this article.

Protein tyrosine phosphatase receptor type Q in cerebrospinal fluid reflects ependymal cell dysfunction and is a potential biomarker for adult chronic hydrocephalus.

BACKGROUND AND PURPOSE: Protein tyrosine phosphatase receptor type Q (PTPRQ) was extracted from the cerebrospinal fluid (CSF) of patients with probable idiopathic normal-pressure hydrocephalus (iNPH) by proteome analysis. We aimed to assess the feasibility of using CSF PTPRQ concentrations for the additional diagnostic criterion of iNPH in Japanese and Finnish populations. METHODS: We compared PTPRQ concentrations among patients with probable iNPH and neurologically healthy individuals (normal control [NC] group), patients with normal-pressure hydrocephalus (NPH) of acquired and congenital/developmental aetiologies, patients with Alzheimer's disease and patients with Parkinson's disease in a Japanese analysis cohort. A corresponding iNPH group and NC group in a Finnish cohort was used for validation. Patients in the Finnish cohort who underwent biopsy were classified into two groups based on amyloid and/or tau deposition. We measured PTPRQ expression levels in autopsied brain specimens of iNPH patients and the NC group. RESULTS: Cerebrospinal fluid PTPRQ concentrations in the patients with NPH of idiopathic, acquired and congenital/developmental aetiologies were significantly higher than those in the NC group and those with Parkinson's disease, but iNPH showed no significant differences when compared with those in the Alzheimer's disease group. For the patients with iNPH, the area under the receiver-operating characteristic curve was 0.860 in the Japanese iNPH and 0.849 in the Finnish iNPH cohorts. Immunostaining and in situ hybridization revealed PTPRQ expression in the ependymal cells and choroid plexus. It is highly possible that the elevated PTPRQ levels in the CSF are related to ependymal dysfunction from ventricular expansion. CONCLUSIONS: Cerebrospinal fluid PTPRQ levels indicated the validity of this assay for auxiliary diagnosis of adult chronic hydrocephalus.

Effects of preemptive analgesia with intravenous acetaminophen on postoperative pain relief in patients undergoing third molar surgery: a prospective, single-blind, randomized controlled trial.

BACKGROUND: The efficacy of preemptive analgesia in managing postoperative pain remains controversial. The aim of this study was to compare the efficacy of intravenous (IV) acetaminophen administered before or immediately after the surgical extraction of an impacted mandibular third molar. MATERIAL AND METHODS: This prospective randomized clinical trial included 120 patients. The patients were assigned to one of three groups: the preoperative-treatment group (pre-group), which received 1000 mg of IV acetaminophen 20 min before surgery; the postoperative-treatment group (post-group), which received 1000 mg of IV acetaminophen after surgery; the no-treatment group (control-group), which did not receive any analgesic. Rescue analgesic (60 mg loxoprofen) was issued to each patient, with instructions on self-administration if needed. For the rescue medication usage, the time of first loxoprofen usage and the total amount of loxoprofen consumption were obtained for a 17-hour period after surgery. We measured pain using the visual analogue scale at 1 hour and at 2, 3, 4, 5, and 15 hours after surgery. RESULTS: There was no significant difference in pain level among the three groups at any time interval. However, the pre-group demonstrated significantly lower rescue analgesic consumption and longer time until initial administration. CONCLUSIONS: Administration of IV acetaminophen before third molar surgery provides more effective pain control than postoperative administration and no treatment.

Difference in Freezing Tolerance Between Young Potato Plants Derived From Tissue Culture Plantlets and Seed Tubers.

BACKGROUND: Although potato as a crop is commercially grown from seed tubers, plants grown from tissue culture plantlets are often used in physiological studies including freezing tolerance determination. OBJECTIVE: This study aimed to examine the effects of the source of plants on freezing tolerance of potato plants at young developmental stages. MATERIALS AND METHODS: We compared freezing tolerance and contents of soluble proteins and sugars of Solanum tuberosum plants derived from tissue culture with those derived from tubers before and after cold acclimation. RESULTS: Tuber-derived plants showed significantly higher freezing tolerance than tissue-culture-derived plants after cold acclimation, although non-acclimated plants did not show any marked differences. Soluble protein contents were higher in tuber-derived plants regardless of cold acclimation. Sucrose content increased to a higher level in tuber-derived plants after cold acclimation. CONCLUSION: These results suggest that source of plant tissue can have a significant effect on the response of young potato plants to freezing stress and that the use of tissue culture plants in freezing tolerance studies may not accurately reflect the frost tolerance of commercially grown plants.

Importance of absorbable surgical sutures for the prevention of stitch abscess after surgery in patients with oral squamous cell carcinoma.

BACKGROUND: To elucidate the significance of absorbable surgical sutures in the occurrence of stitch abscess after surgery in patients with oral squamous cell carcinoma (SCC). MATERIAL AND METHODS: The subjects were 251 patients who underwent excision and/or reconstruction and/or neck dissection for oral SCC using absorbable surgical sutures. Detection rates and characteristics of patients with stitch abscess were retrospectively evaluated by comparing between our present and previous data. RESULTS: There was only one stitch abscess among the 251 patients. A significant difference in the incidence of stitch abscess was found between the present data and our previous data. Of course, no significant correlations were found between the occurrence of stitch abscess using absorbable surgical sutures and the various factors seen in our previous analysis. CONCLUSIONS: A complete switch of surgical sutures from silk to absorbable surgical sutures is needed for surgery in patients with oral SCC.

Economic evaluation of a preemptive treatment strategy for invasive fungal infection in neutropenic patients with hematological diseases.

We compared the expected medical costs of empirical and preemptive treatment strategies for invasive fungal infection in neutropenic patients with hematological diseases. Based on the results of two clinical trials with different backgrounds reported by Oshima et al. [J Antimicrob Chemother 60(2):350-355; Oshima study] and Cordonnier et al. [Clin Infect Dis 48(8):1042-1051; PREVERT study], we developed a decision tree model that represented the outcomes of empirical and preemptive treatment strategies, and estimated the expected medical costs of medications and examinations in the two strategies. We assumed that micafungin was started in the empirical group at 5 days after fever had developed, while voriconazole was started in the preemptive group only when certain criteria, such as positive test results of imaging studies and/or serum markers, were fulfilled. When we used an incidence of positive test results of 6.7 % based on the Oshima study, the expected medical costs of the empirical and preemptive groups were 288,198 and 150,280 yen, respectively. Even in the case of the PREVERT study, in which the incidence of positive test results was 32.9 %, the expected medical costs in the empirical and preemptive groups were 291,871 and 284,944 yen, respectively. A sensitivity analysis indicated that the expected medical costs in the preemptive group would exceed those in the empirical group when the incidence of positive test results in the former was over 34.4 %. These results suggest that a preemptive treatment strategy can be expected to reduce medical costs compared with empirical therapy in most clinical settings.

Risk factors for pre- and post-engraftment bloodstream infections after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Bloodstream infections (BSI) are frequently observed after allogeneic hematopoietic stem cell transplant (HSCT), and could cause morbidity and mortality. METHODS: We retrospectively evaluated the incidence, characteristics of, and risk factors for BSI at both pre- and post-engraftment in 209 adult HSCT patients at our institute between June 2006 and December 2013. The median age at transplantation was 45 years (range, 15-65). A total of 122 patients received bone marrow, 68 received peripheral blood stem cells, and 19 received umbilical cord blood. RESULTS: The cumulative incidences of pre- and post-engraftment BSI were 38.9% and 17.2%, respectively. Nine patients had both pre- and post-engraftment BSI. In the pre- and post-engraftment periods, respectively, 67.4% and 84.1% of isolates were gram-positive bacteria (GPB), 28.3% and 11.4% were gram-negative bacteria (GNB), and 4.3% and 4.5% were fungi. Coagulase-negative staphylococci were the most commonly isolated GPB, while Stenotrophomonas maltophilia and Pseudomonas aeruginosa were the most commonly isolated GNB. Pre-engraftment BSI was associated with an increased risk of death. Overall survival at day 180 for patients with or without pre-engraftment BSI was 70.0% and 82.7%, respectively (P = 0.02). CONCLUSIONS: Risk factors for BSI in the pre-engraftment period were the interval between diagnosis and transplantation (261 days or more), engraftment failure, and high-risk disease status at HSCT in a multivariate analysis. No significant risk factor for BSI in the post-engraftment period was identified by a univariate analysis. These findings may be useful for deciding upon empiric antibacterial treatment for HSCT recipients.

Allotype analysis to determine the origin of cytomegalovirus immunoglobulin-G after allogeneic stem cell transplantation.

BACKGROUND: Cytomegalovirus (CMV) reactivation still remains a major problem following allogeneic hematopoietic stem cell transplantation (HSCT). PATIENTS AND METHODS: In this study, we analyzed an immunoglobulin allotype, IgG1m(f), in CMV-seropositive HSCT recipients and their donors to distinguish donor-derived antibody from recipient-derived antibody. Eight donor-recipient pairs were informative regarding the appearance of donor-derived immunoglobulin-G (IgG), as the recipients were homozygous null for the IgG1m(f) allotype and the donors were IgG1m(f) positive. In these patients, total IgG, IgM, and allotype-specific IgG against CMV were measured by enzyme-linked immunosorbent assay. All subjects were monitored for at least 9 months after HSCT with (n = 5) or without (n = 3) CMV reactivation. RESULTS: Donor-derived CMV IgG tended to be elevated earlier in patients with CMV-seropositive donors than in those with CMV-seronegative donors. In 1 patient with a CMV-negative donor, donor-derived CMV IgG was not detected until late CMV reactivation. In 3 patients without CMV reactivation, donor-derived CMV IgG was also elevated within 1-6 months after HSCT. CONCLUSION: In conclusion, the CMV serostatus of the donor may be related to the timing of the appearance of donor-derived CMV IgG and the reconstitution of humoral immunity against CMV, regardless of the CMV antigenemia level after HSCT.

Persistence of recipient-derived as well as donor-derived clones of cytomegalovirus pp65-specific cytotoxic T cells long after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Cytomegalovirus (CMV)-specific CD8(+) cytotoxic T lymphocytes (CMV-CTLs) play a crucial role in preventing CMV disease. However, the actual in vivo dynamics of CMV-CTL clones after allogeneic hematopoietic stem cell transplantation (alloHCT) are still unclear. METHODS: Using a single-cell T-cell receptor repertoire analysis, we monitored clones and chimerism of CMV-CTLs in 3 CMV-seropositive alloHCT recipients from CMV-seronegative donors, with or without CMV reactivation. RESULTS: Nearly all of the CMV-CTLs during follow-up were CD45RA(-) CCR7(-) effector memory/CD45RA(+) CCR7(-) effector T cells, and were highly matured. In each case, the use of BV gene families was restricted, especially in BV5, 7, 28, and 29. Although no common predominant CMV-CTL clones were found, several shared motifs of complementarity-determining region-3 were identified among the 3 cases; QGA in all, TGE and TDT in Case 1 and Case 2, and RDRG in Case 2 and Case 3. In all cases, CMV-CTL clones that were detected for the first time after alloHCT persisted as the dominant clones. In Case 1, without CMV reactivation, recipient-derived CMV-CTLs exclusively persisted as a dominant clone, while all CMV-CTLs in the other 2 cases, with CMV reactivation, were donor derived. CONCLUSION: Clone monitoring and chimerism analyses should help to further clarify novel aspects of immuno-reconstitution after alloHCT.

Low-dose acyclovir prophylaxis for the prevention of herpes simplex virus disease after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Currently, acyclovir (ACV) at 1000 mg/day is widely used as prophylaxis in the early phase of hematopoietic stem cell transplant (HSCT) in Japan. However, low-dose ACV (200 mg/day) has been shown to prevent varicella zoster virus reactivation in the middle and late phases of HSCT. METHODS: Therefore, in this study, we decreased the dose of ACV to 200 mg/day in the early phase after HSCT. We analyzed 93 consecutive herpes simplex virus (HSV)-seropositive patients who underwent allogeneic HSCT for the first time in our center between June 2007 and December 2011. RESULTS: Before August 2009, 38 patients received oral ACV at 1000 mg/day (ACV1000) until day 35 after HSCT, whereas 55 patients received oral ACV at 200 mg/day (ACV200) after September 2009. We compared the cumulative incidence of HSV infection in the 2 groups. Oral ACV was changed to intravenous administration because of intolerance in 66% and 45% of the patients in the ACV1000 and ACV200 groups, respectively (P = 0.060). The probability of severe stomatitis (Bearman grade II-III) was 76% and 60% in the ACV1000 and ACV200 groups, respectively (P = 0.12). The number of patients who developed HSV disease before day 100 after HSCT was 0 in the ACV1000 group and 2 in the ACV200 group, with a cumulative incidence of 3.6% (P = 0.43). HSV disease in the latter 2 patients was limited to the lips and tongue and was successfully treated with ACV or valacyclovir at a treatment dose. CONCLUSION: ACV at 200 mg/day appeared to be effective for preventing HSV disease in the early phase after HSCT.

Abrupt change of Antarctic moisture origin at the end of Termination II.

The deuterium excess of polar ice cores documents past changes in evaporation conditions and moisture origin. New data obtained from the European Project for Ice Coring in Antarctica Dome C East Antarctic ice core provide new insights on the sequence of events involved in Termination II, the transition between the penultimate glacial and interglacial periods. This termination is marked by a north-south seesaw behavior, with first a slow methane concentration rise associated with a strong Antarctic temperature warming and a slow deuterium excess rise. This first step is followed by an abrupt north Atlantic warming, an abrupt resumption of the East Asian summer monsoon, a sharp methane rise, and a CO(2) overshoot, which coincide within dating uncertainties with the end of Antarctic optimum. Here, we show that this second phase is marked by a very sharp Dome C centennial deuterium excess rise, revealing abrupt reorganization of atmospheric circulation in the southern Indian Ocean sector.

Percutaneous shunt vessel embolisation with Amplatzer vascular plugs II and IV in the treatment of dogs with splenophrenic shunts: four cases (2019-2022).

OBJECTIVES: To describe the treatment of four dogs with splenophrenic shunts using percutaneous shunting vessel embolisation with Amplatzer vascular plugs II and IV and provide information on their clinical outcomes. MATERIALS AND METHODS: Dogs with splenophrenic shunts treated at a veterinary hospital from January 2019 to December 2022 were identified through a medical record search. RESULTS: Six dogs with splenophrenic shunts were identified. Two dogs were excluded because they were treated with laparoscopic surgery. Four underwent percutaneous shunting vessel embolization with Amplatzer vascular plugs and were included in the case series. A sheath was placed in the left external jugular vein and a balloon catheter was advanced to the shunting vessel under fluoroscopy. Portal vein pressure was confirmed to be within an acceptable range during temporary balloon occlusion. Based on preoperative CT angiography and intraoperative contrast examination, Amplatzer vascular plugs II were selected for two dogs and IV were selected for two dogs. Under fluoroscopy, the plug was deployed into the shunting vessel, and angiography confirmed occlusion. In all cases, the increase in portal pressure after temporary occlusion was within the acceptable range, and complete occlusion of blood flow was possible with a single plug. There were no major procedure-related complications. No dogs developed post-ligation seizures or signs of portal hypertension. In addition, improvements in ammonia values were observed in all cases. CLINICAL SIGNIFICANCE: Percutaneous splenophrenic shunt embolisation using Amplatzer vascular plugs II and IV is technically feasible in dogs, and assessed by intra-procedure angiography, a single plug completely obstructed blood flow in all dogs. Based on the literature search, this is the first report describing Amplatzer vascular plugs for the treatment of splenophrenic shunts.

Subzero saline chilling with or without prechilling in icy water improved chilling efficiency and meat tenderness of broiler carcasses.

Freshly slaughtered carcasses need to be chilled to improve product quality, meat safety, and processing efficiency. This research investigated the effect of subzero saline chilling (SSC) on broiler carcasses with or without prechilling in icy water. Water immersion chilling at 0.5°C (WIC) or SSC at 4% NaCl/-2.41°C (SSC) was a major chilling step. For the combination of pre- and postchilling, the warm water immersion chilling (WWIC) at 10°C was used as prechilling and the WIC as postchilling (WWIC-WIC), and WIC was used as prechilling and the SSC as postchilling (WIC-SSC). The internal temperature of breast fillets was monitored during chilling. Carcasses in a prechiller were transported to a postchiller when their internal temperature reached 15°C. Chilling was completed when the carcass temperature reached 4.4°C or below, and breast fillets were harvested at 3-h postmortem to measure the pH and sarcomere length. Color (L*, a*, and b*) values were evaluated on both breast skin and skinless breast surfaces. Meat tenderness was evaluated using the breast fillets after overnight storage and cooking to an internal temperature of 76°C. The carcasses in the SSC and WIC-SSC showed shorter chilling times (85-91 min) than those (100-144 min) of WIC and WWIC-WIC. A higher chilling yield was observed for the carcasses in WIC-SSC, and a lower cooking yield was seen for the carcasses in WWIC-WIC than other chilling methods (P < 0.05). The breast fillets of broilers in the SSC and WIC-SSC showed lower shear forces and longer sarcomere length than the WIC and WWIC-WIC. No difference was found for L* and a* values, while lower b* value was observed in the SSC than the other chilling methods (P < 0.05). Based on these results, chilling of broiler carcasses in the SSC (4% NaCl/-2.41°C) with or without prechilling in WIC at 0.5°C significantly improved chilling efficiency and meat tenderness, with minor color changes on carcasses.

An example of governance for AI in health services from Aotearoa New Zealand.

Artificial Intelligence (AI) is undergoing rapid development, meaning that potential risks in application are not able to be fully understood. Multiple international principles and guidance documents have been published to guide the implementation of AI tools in various industries, including healthcare practice. In Aotearoa New Zealand (NZ) we recognised that the challenge went beyond simply adapting existing risk frameworks and governance guidance to our specific health service context and population. We also deemed prioritising the voice of Maori (the indigenous people of Aotearoa NZ) a necessary aspect of honouring Te Tiriti (the Treaty of Waitangi), as well as prioritising the needs of healthcare service users and their families. Here we report on the development and establishment of comprehensive and effective governance over the development and implementation of AI tools within a health service in Aotearoa NZ. The implementation of the framework in practice includes testing with real-world proposals and ongoing iteration and refinement of our processes.

Combined Exercise and Education Program: Effect of Smaller Group Size and Longer Duration on Physical Function and Social Engagement among Community-Dwelling Older Adults.

Background: Exercise, education, and social engagement are critical interventions for older adults for a healthy life expectancy and to improve their physical function. Objective: To conduct a combined exercise and education (CEE) program for improved social engagement and physical function of older adults. Design: Based on a short-term program we conducted in our previous study, in this study, the program was conducted for half the number of participants of the earlier study but for a longer duration. Setting: A community of older adults in Ami, Japan, was the setting of the study. Participants: 23 healthy older adults >65 years living in the community were the participants in the study. Interventions: Five 80-minute sessions conducted once in two weeks comprised 60-min exercise instruction and 20-min educational lectures per session on health. We examined the improvement in physical and social engagement before and after participation. Physical function and health-related questionnaire data were collected before and after the program. Results: Data analysis from 15 participants showed improved physical performance but no effect on social engagement. Conclusions: A higher program frequency, rather than program duration, may be vital to improving exercise performance and social engagement and maximizing the effects of high group cohesion in small groups. Further studies are needed to develop more effective interventions to extend healthy life expectancy.

Effects of stocking hatchery fish on the phenotype of indigenous populations in the amago salmon Oncorhynchus masou ishikawae in Japan.

The expression of colour marks (parr marks, red and black spots) of the amago salmon Oncorhynchus masou ishikawae was compared with microsatellite information, to see the effects of stocking hatchery fish on the phenotype of indigenous populations, which face extinction through extensive stocking. A Bayesian-based assignment test suggested introgression of two exotic clusters into one indigenous cluster in the stocked area and its vicinity. The number of parr marks was significantly higher in one hatchery-origin population, which exclusively comprised one exotic cluster. An increased number of red spots in stocked hatchery fish was probably a consequence of hatchery feeding conditions. The number of black spots was correlated with body size in many populations, except for hatchery and heavily introgressed populations. Coefficients of correlation and regression of black spots with body size, which were largest in indigenous populations, decreased with an increase of introgression by hatchery fish. As indigenous populations have low genetic diversity with high relatedness, it was inferred that the height of correlation and regression coefficients in black spots is caused by high genetic homogeneity and fixation of alleles in loci related to the increase of black spots, both of which might have collapsed with introgression by hatchery fish. These results suggest the possibility that introgression by stocked fish causes a change of phenotype in indigenous populations.

Adenoviruses-mediated transduction of human oesophageal carcinoma cells with the interferon-λ genes produced anti-tumour effects.

BACKGROUND: Interferon-λs (IFN-λs) are novel cytokines with multiple functions, like IFN-α and -ß. We examined possible anti-tumour effects produced by adenoviruses bearing the IFN-λ1 or -λ2 gene (Ad/IFN-λ) with the type-35 fibre-knob structure. METHODS: Proliferation of oesophageal carcinoma cells transduced with Ad/IFN-λ and mechanisms of the inhibited growth were investigated. RESULTS: Transduction with Ad/IFN-λ upregulated the expression of the class I antigens of the major histocompatibility complexes and induced the growth suppression. Increased sub-G1 populations and the cleavage of caspase-3 and poly (ADP-ribose) polymerase were detected in IFN-λ-sensitive YES-2 and T.Tn cells. The cell death was accompanied by cytoplasmic cytochrome C and increased cleaved caspase-9 and Bax expression, suggesting mitochondria-mediated apoptosis. Adenovirus/IFN-λ-infected YES-2 cells subsequently reduced the tumourigenicity. Adenovirus/IFN-λ-infected fibroblasts, negative for the IFN-λ receptors, induced death of YES-2 or T.Tn cells that were co-cultured. Inoculation of YES-2 cells in nude mice, when mixed with the Ad/IFN-λ-infected fibroblasts, resulted in retardation of the tumour growth. The growth suppression was not linked with upregulated CD69 expression on natural killer cells or increased numbers of CD31-positive cells. CONCLUSION: Adenovirus/IFN-λ induced apoptosis, and fibroblast-mediated delivery of IFN-λs is a potential cancer treatment by inducing direct cell death of the target carcinoma.

Impact of the Coronavirus Disease 2019 Outbreak on Activity and Exercise Levels among Older Patients.

OBJECTIVES: This study aimed to clarify the impact of the coronavirus disease 2019 outbreak on the levels of activity among older patients with frailty or underlying diseases. A total of 175 patients (79.0±7.0 years) undergoing outpatient or home-based rehabilitation, stratified into groups, based on frailty status. The percentage of patients who went out at least once a week decreased after the outbreak from 91% to 87%, from 65% to 46%, and from 47% to 36% in the non-frail, frail, and nursing care requirement groups, respectively. The proportion of older patients participating in exercise during the outbreak was 75%, 51%, and 41% in the non-frail, frail, and nursing care requirement groups, respectively. The proportion of older patients participating in voluntary exercise after instruction was lowest in the frail group (35%). Older patients with frailty are susceptible to the negative effects of refraining from physical activity and require careful management.