Predictive characteristics of male fertility in alpacas with special reference to seminal NGF.

Recent studies document the LH-releasing pathway of nerve growth factor (NGF) in male camelids and that the LH response to seminal NGF is associated with elevated plasma testosterone concentration. Results provide rationale for the hypothesis that NGF in semen is associated with male fertility. In Experiment 1, the association between the amount of NGF in the ejaculate and characteristics of the male reproductive system was examined in alpacas. The concentration of NGF was measured by radioimmunoassay in semen samples collected from male alpacas (n = 47) and correlated with sperm morphology and motility, and measurements of the male reproductive anatomy. Most ejaculates had NGF concentrations that, based on previous studies, triggered ovulation in female camelids, however, we only found a positive correlation between NGF concentration with sperm concentration, thread formation and total NGF, and a negative correlation with pH. In Experiment 2, a retrospective analysis was carried out to determine if breeding performance during the previous season was related to recent concentrations of seminal NGF in male alpacas (n = 22). Birth rates tended to be correlated with sperm concentration and total amount of NGF in the ejaculate (P = 0.09). Experiment 3 was a prospective study to determine the relationship between seminal NGF (n = 8 male alpacas) and ovulation and pregnancy rates in a breeding trial. No association was detected between seminal NGF concentration and ovulation rate, pregnancy rate, or LH response in the female. We conclude that among the breeding males used in our study, the abundance of seminal NGF was correlated with sperm concentration and thread formation, however, it was not predictive of male fertility in alpacas. Examination of males not previously selected as breeding stock may be expected to include a broader range of seminal NGF and provide a more comprehensive understanding of the relationship between seminal NGF and male fertility.

Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099.

PURPOSE: The Southwest Oncology Group (SWOG) coordinated an Intergroup study with the participation of Radiation Therapy Oncology Group (RTOG), and Eastern Cooperative Oncology Group (ECOG). This randomized phase III trial compared chemoradiotherapy versus radiotherapy alone in patients with nasopharyngeal cancers. MATERIALS AND METHODS: Radiotherapy was administered in both arms: 1.8- to 2.0-Gy/d fractions Monday to Friday for 35 to 39 fractions for a total dose of 70 Gy. The investigational arm received chemotherapy with cisplatin 100 mg/m2 on days 1, 22, and 43 during radiotherapy; postradiotherapy, chemotherapy with cisplatin 80 mg/m2 on day 1 and fluorouracil 1,000 mg/m2/d on days 1 to 4 was administered every 4 weeks for three courses. Patients were stratified by tumor stage, nodal stage, performance status, and histology. RESULTS: Of 193 patients registered, 147 (69 radiotherapy and 78 chemoradiotherapy) were eligible for primary analysis for survival and toxicity. The median progression-free survival (PFS) time was 15 months for eligible patients on the radiotherapy arm and was not reached for the chemo-radiotherapy group. The 3-year PFS rate was 24% versus 69%, respectively (P < .001). The median survival time was 34 months for the radiotherapy group and not reached for the chemo-radiotherapy group, and the 3-year survival rate was 47% versus 78%, respectively (P = .005). One hundred eighty-five patients were included in a secondary analysis for survival. The 3-year survival rate for patients randomized to radiotherapy was 46%, and for the chemoradiotherapy group was 76% (P < .001). CONCLUSION: We conclude that chemoradiotherapy is superior to radiotherapy alone for patients with advanced nasopharyngeal cancers with respect to PFS and overall survival.

Physicians' mental health and coping during the COVID-19 pandemic: One year exploration.

Numerous cross-sectional studies have examined physicians' health and coping during the COVID-19 pandemic, while longitudinal studies are lacking. This study explores the progression over one year of physicians' physical and mental health symptoms, their strategies used to cope and discusses coping strategies in relation to physical and mental health symptoms. Two surveys, one year apart, exploring physicians' physical, mental health symptoms and employed coping strategies were sent to all physicians practicing in the province of Saskatchewan, Canada. A total of 117 physicians participated in Round I (RI) (November 2020-January 2021) and 158 participated in Round II (RII) (October 2021-February 2022). Physicians' physical and mental health symptoms remained high, irrespective of their specialty or COVID-19 exposure. COVID-related Post-Traumatic Stress Disorder increased by five times at RII (p = 0.02). In RI anxiety was most prevalent in middle-aged females. In RII depression was most prevalent in physicians with no children. Most coping was adaptive (90%) and included Behavioural, Relational, Cognitive, Spiritual, and Interventional strategies. After one-year, Spiritual coping decreased, while Interventional coping increased by eight times (p = 0.01). Despite efforts to employ adaptive coping, physicians' rates of psychological and physical health difficulties remained high or worsened over one year, offering insight into the protracted health care crisis, and the need for solutions. Our observation of physicians' needs for additional supports, camaraderie and appreciation as well as the shift in coping strategies as the pandemic progressed, offer targets for interventions meant to promote recovery.

Anti-inflammatory, procollagen, and wound repair properties of topical insulin gel.

Diabetes mellitus is associated with impaired wound healing. The topical use of insulin is a promising therapy because it may favor all phases of the wound healing process. This study aimed to investigate the therapeutic outcomes of insulin gel in wounds of hyperglycemic mice. After diabetes induction, a 1-cm2 full-thickness wound was created on each animal's dorsum. The lesions were treated daily for 14 days with insulin gel (insulin group) or vehicle gel without insulin (vehicle group). Tissue samples were extracted on days 4, 7, 10, and 14 after the creation of the lesion. The samples were analyzed with hematoxylin/eosin and Sirius red staining, immunohistochemistry, Bio-Plex immunoassays, and western blotting. Insulin gel favored re-epithelialization at day 10 and increased the organization and deposition of collagen. Additionally, it modulated the expression of cytokines (interleukin (IL)-4 and IL-10) and increased the expression of arginase I, VEGF receptor 1, and VEGF on day 10. Activation of the insulin signaling pathway occurred via IRß, IRS1, and IKK on day 10 and activation of Akt and IRS1 on day 14. These results suggested that insulin gel improved wound healing in hyperglycemic mice by modulating the expression of inflammatory factors, growth factors, and proteins of the insulin signaling pathway.

Doctors' Professional and Personal Reflections: A Qualitative Exploration of Physicians' Views and Coping during the COVID-19 Pandemic.

Numerous studies have examined the risks for anxiety and depression experienced by physicians during the COVID-19 pandemic. Still, qualitative studies investigating physicians' views, and their discovered strengths, are lacking. Our research fills this gap by exploring professional and personal reflections developed by physicians from various specialties during the pandemic. Semi-structured interviews were conducted with physicians practicing in the province of Saskatchewan, Canada, during November 2020-July 2021. Thematic analysis identified core themes and subthemes. Seventeen physicians, including nine males and eight females, from eleven specialties completed the interviews. The pandemic brought to the forefront life's temporality and a new appreciation for life, work, and each other. Most physicians found strength in values, such as gratitude, solidarity, and faith in human potential, to anchor them professionally and personally. A new need for personal fulfilment and hybrid care emerged. Negative feelings of anger, fear, uncertainty, and frustration were due to overwhelming pressures, while feelings of injustice and betrayal were caused by human or system failures. The physicians' appreciation for life and family and their faith in humanity and science were the primary coping strategies used to build adaptation and overcome negative emotions. These reflections are summarized, and implications for prevention and resilience are discussed.

Childhood trauma as a mediator between attachment and recidivism risk: A study of Canadian offenders with mental disorders.

The current study aimed to explore the relationships between attachment and childhood trauma on recidivism risk in a sample of Canadian offenders with mental disorder (OMDs). N = 56 OMDs completed the Adverse Childhood Experiences (ACE) questionnaire, a measure of adult attachment (Experiences in Close Relationships Scale), and interview to determine recidivism risk (Level of Service/Case Management Inventory; LS/CMI). The variables of interest had small to moderate correlations. Multivariable regression analysis found that ACE scores but not attachment insecurity were associated with LS/CMI scores. Mediation analyses demonstrated that ACE scores fully mediated the association between attachment anxiety and attachment avoidance and recidivism risk. Results demonstrate that as exposure to diverse ACEs increased so did the risk to recidivate and this exposure mediated the relationship between attachment insecurity and recidivism risk. This study highlights the necessity of addressing both attachment insecurity and the experience of ACE when providing psychiatric services to OMDs.

Development and Biodistribution of a Nerve Growth Factor Radioactive Conjugate for PET Imaging.

PURPOSE: The purpose of these studies was to develop a nerve growth factor (NGF) radiometal-chelator conjugate to determine the biodistribution and brain uptake of NGF by positron emission tomography/computerized tomography (PET-CT). PROCEDURES: Purified NGF from llama seminal plasma was conjugated with FITC, and the chelator NOTA or DFO. NGF conjugates were evaluated for bioactivity. NOTA- and DFO-conjugated NGF were radiolabeled with gallium-68 or zirconium-89 ([68 Ga]GaCl3, half-life = 68 min; [89Zr]Zr(oxalate)4, half-life = 3.3 days). [89Zr]Zr-NGF was evaluated for biodistribution (0.5, 1, or 24 h), PET imaging (60 min), and brain autoradiography in mice. RESULTS: Cell-based in vitro assays confirmed that the NGF conjugates maintained NGF receptor-binding and biological activity. Zirconium-89 and gallium-68 radiolabeling showed a high efficiency; however, only[89Zr]Zr-NGF was stable in vitro. Biodistribution studies showed that, as with most small proteins < 70 kDa, [89Zr]Zr-NGF uptake was predominantly in the kidney and was cleared rapidly with almost complete elimination of NGF at 24 h. Dynamic PET imaging from 0-60 min showed a similar pattern to ex vivo biodistribution with some transient liver uptake. Interestingly, although absolute brain uptake was very low, at 24 h after treatment, cerebral cortex uptake was higher than any other brain area examined and blood. CONCLUSIONS: We conclude that conjugation of DFO to NGF through a thiourea linkage allows effective radiolabeling with zirconium-89 while maintaining NGF bioactivity. Following intravenous administration, the radiolabeled NGF targets non-neuronal tissues (e.g., kidney, liver), and although absolute brain uptake was very low, the brain uptake that was observed was restricted to the cortex.

Exploring the Relationship Between Attachment and Pathological Personality Trait Domains in an Outpatient Psychiatric Sample.

ABSTRACT: The current study investigates the relationship between insecure attachment and pathological personality trait domains in a sample of psychiatric outpatients. Participants ( N = 150) completed measures for attachment and personality. Bivariate correlations and multiple regression analyses investigated the extent to which insecure attachment and personality pathology were associated. Insecure attachment positively correlated with overall personality pathology, with attachment anxiety having a stronger correlation than attachment avoidance. Distinct relationships emerged between attachment anxiety and negative affectivity and attachment avoidance and detachment. Insecure attachment and male sex predicted overall personality pathology, but only attachment anxiety predicted all five trait domains. Insecure attachment might be a risk factor for pathological personality traits. Assessing attachment in clinical contexts and offering attachment-based interventions could benefit interpersonal outcomes.

Anti-inflammatory, procollagen, and wound repair properties of topical insulin gel

Diabetes mellitus is associated with impaired wound healing. The topical use of insulin is a promising therapy because it may favor all phases of the wound healing process. This study aimed to investigate the therapeutic outcomes of insulin gel in wounds of hyperglycemic mice. After diabetes induction, a 1-cm2 full-thickness wound was created on each animal's dorsum. The lesions were treated daily for 14 days with insulin gel (insulin group) or vehicle gel without insulin (vehicle group). Tissue samples were extracted on days 4, 7, 10, and 14 after the creation of the lesion. The samples were analyzed with hematoxylin/eosin and Sirius red staining, immunohistochemistry, Bio-Plex immunoassays, and western blotting. Insulin gel favored re-epithelialization at day 10 and increased the organization and deposition of collagen. Additionally, it modulated the expression of cytokines (interleukin (IL)-4 and IL-10) and increased the expression of arginase I, VEGF receptor 1, and VEGF on day 10. Activation of the insulin signaling pathway occurred via IRβ, IRS1, and IKK on day 10 and activation of Akt and IRS1 on day 14. These results suggested that insulin gel improved wound healing in hyperglycemic mice by modulating the expression of inflammatory factors, growth factors, and proteins of the insulin signaling pathway.

Predictors of the ovarian superstimulatory response and oocyte collection in prepubertal heifers.

The objectives were to investigate the relationships between antral follicle counts and plasma AMH and FSH at the time of follicular wave emergence in prepubertal calves, and to determine the effects of age and duration of gonadotropin treatment on the ovarian superstimulatory response in pre- and post-pubertal heifers. Hereford crossbred prepubertal (Replicate 1 and 2, n = 20) and post-pubertal heifers (Replicates 1, n = 8; Replicate 2, n = 8) were assigned randomly to 2 treatment groups and given FSH for either 4 or 7 d (25 mg pFSH im at 12-h intervals). Prepubertal heifers were first treated at 4 mo and again at 7 mo of age. Blood samples were collected immediately before the first FSH administration, that was initiated 36 h after follicular ablation. An LH treatment (12.5 mg im) was given 12 h after the last FSH injection. Follicular fluid and cumulus-oocyte complexes (COC) were collected 24 h after LH treatment. At wave emergence, the number of follicles ≥1 mm (AFC, 31.1 ± 4.0 vs 16.2 ± 1.8; P < 0.001) and the plasma concentrations of AMH (606.4 ± 90.5 vs 279.6 ± 28.3 pg/mL; P = 0.001) were higher at 4 than at 7 mo of age, while plasma FSH concentrations did not differ between ages. At oocyte collection, a higher number of follicles ≥6 mm were observed in prepubertal calves at 4 mo of age and post-pubertal heifers than in calves at 7 mo of age (32.4 ± 5.4 and 22.0 ± 2.3 vs 14.9 ± 2.0, respectively; P = 0.003). Intrafollicular concentrations of estradiol were lower (23.7 ± 4.5 vs 144.0 ± 29.5 ng/mL; P < 0.0001) and of progesterone tended to be higher (217.5 ± 29.3 vs 157.0 ± 33.9 ng/mL; P = 0.07) in the 7- than in the 4-d groups. A greater number of COC was collected from calves at 4 mo of age and heifers than the 7-mo-old calves (13.4 ± 2.6 and 6.0 ± 1.0 vs 5.8 ± 1.1, respectively; P = 0.008). Overall, the 7-d FSH treatment tended to result in a greater proportion of expanded COC than the 4-d treatment in calves (50.1 ± 7.7 vs 31.9 ± 6.8%; P = 0.07). In summary, there was a positive relationship between AFC and plasma AMH concentrations at the time of wave emergence. A higher AFC was observed in calves at 4- than 7-mo of age, which resulted in greater ovarian response to gonadotropin treatment. Following an exogenous LH stimulus, COC maturation rates were greater in the 7-d than in the 4-d FSH treatment groups, resulting in collection of a higher proportion of fully expanded COC.

Microbiome profiles of non-responding and responding paired periodontitis sites within the same participants following non-surgical treatment.

Aim: Periodontitis is a site-specific, chronic disease treated by non-surgical debridement of subgingival plaque. We aimed to determine the microbiome of sites that did not respond to this treatment (NR) compared with paired good responding (GR) sites before and after treatment. Materials and methods: In a longitudinal cohort study, clinical parameters of disease and biological samples were taken prior to and 3 months after treatment. Twelve NR sites from six participants were paired with GR sites within the same participant. Subgingival plaque samples were subjected to bacterial community analysis using 16S rRNA gene sequencing. Results: There were no significant differences in clinical parameters and microbial communities at baseline between GR and NR sites. Bacterial communities in deep pockets were dominated by a small number of species, notably Porphyromonas gingivalis and Treponema denticola. In NR sites three months after treatment there was no significant change in bacterial composition whilst there was a collapse in the abundance of pathobionts in GR sites. Conclusion: NR sites were not identifiable prior to treatment by clinical or microbiological parameters. Treatment failed to disrupt pathogenic bacterial community in NR sites. Targeted suppression of particular species should be considered to initiate community collapse and aid disease resolution.

Historical reconstruction of the population dynamics of southern right whales in the southwestern Atlantic Ocean.

Understanding the recovery of whale populations is critical for developing population-management and conservation strategies. The southern right whale (SRW) Eubalena australis was one of the baleen whale species that has experienced centuries of exploitation. We assess here for the first time the population dynamics of the SRW from the southwestern Atlantic Ocean at the regional level to measure numerically the effect of whaling and estimate the population trend and recovery level after depletion. We reconstructed the catch history of whaling for the period 1670-1973 by an extensive review of different literature sources and developed a Bayesian state-space model to estimate the demographic parameters. The population trajectory indicated that the pre-exploitation abundance was close to 58,000 individuals (median = 58,212; 95% CI = 33,329-100,920). The abundance dropped to its lowest abundance levels in the 1830s when fewer than 2,000 individuals remained. The current median population abundance was estimated at 4,742 whales (95% CI = 3,853-6,013), suggesting that the SRW population remains small relative to its pre-exploitation abundance (median depletion P2021 8.7%). We estimated that close to 36% of the SRW population visits the waters of the Península Valdés, the main breeding ground, every year. Our results provide insights into the severity of the whaling operation in the southwestern Atlantic along with the population´s response at low densities, thus contributing to understand the observed differences in population trends over the distributional range of the species worldwide.

The Relationship Between Attachment and Self-Injurious Behaviors in the Child and Adolescent Population: A Systematic Review of the Literature.

Adolescents have high rates of self-injurious behavior (SIB), with suicide being the second leading cause of death. A consistent relationship between individual attachment and SIB was previously found in adult population; however, no such review has been undertaken for the child and adolescent population. A systematic search of PubMED, OVID, and PsychINFO up to March 31, 2020 was performed. Twenty-two articles met the inclusion criteria. Of the 22 articles, 21 found a positive association between attachment insecurity and SIB. Our results show a consistent relationship between attachment insecurity and SIB in children and adolescents, complementing the results found in the adult literature. These findings make a case for preventive strategies aimed at reducing self-injurious behaviors in youth by targeting attachment security.

Alexithymia is a mediating factor in the relationship between adult attachment and severity of depression and social anxiety.

BACKGROUND: Major depressive disorder (MDD) and social anxiety disorder (SAD) are commonly occurring conditions, either alone or together (MDD-SAD). Recent research linked insecure attachment and alexithymia to MDD and/or SAD, indicating that the way affected individuals relate interpersonally and their ability to identify and communicate emotions are pertinent issues. The current study investigated the mediating role of alexithymia in the relationship between insecure attachment and severity of MDD and SAD symptoms. METHOD: Using the SCID-I, participants (N=159) were identified as MDD-only (n=43), MDD-SAD (n=56), or a healthy control (n=60). Participants completed measures of adult attachment, depression, social anxiety and alexithymia (defined as difficulty identifying and describing feelings). A two-step mediation analysis approach recommended by Shrout and Bolger determined if alexithymia mediates the relationship between attachment-depression and attachment-social anxiety. RESULTS: While alexithymia was high in MDD-only and MDD-SAD groups, individuals with MDD-SAD had significantly greater difficulty describing feelings. Alexithymia was a full mediator between attachment avoidance and depression, but only a partial mediator between attachment anxiety and depression. Meanwhile, alexithymia was a partial mediator for both attachment dimensions and social anxiety. LIMITATIONS: Causal inferences regarding insecure attachment, alexithymia, and MDD and SAD cannot be assumed given the cross-sectional data. The 'externally oriented thinking' component in alexithymia was also excluded from analyses due to low reliability. CONCLUSION: The results suggest emotional awareness and expression play a role in the illness severity for MDD and SAD-particularly in those with high attachment avoidance, offering a possible target for treatment and prevention strategies.

Demand for regional level III neonatal services is not reduced during national COVID lockdowns.

Following the first peak of the COVID-19 pandemic, reports from around the world suggested a reduction in preterm deliveries during lockdown periods. We reviewed preterm admissions to a large tertiary neonatal unit in inner North East London during two United Kingdom (UK) national lockdowns in 2020 and 2021. We found no evidence of difference in admissions during two national lockdowns compared to previous years. Based on these findings, we recommend that neonatal services remain as vigilant and prepared as ever for the unpredictable nature of preterm birth, and their staff protected to provide this highly specialist care.

Comparison of two intravaginal progesterone-releasing devices in shortened-timed artificial insemination protocols in beef cattle.

Commercially available intravaginal progesterone (P4) devices differ in shape, surface area and P4 load, which may affect the resulting pregnancy per AI (P/AI) following timed-AI (TAI). The objective of this study was to compare two intravaginal P4 devices on estrus rate, follicular dynamics and P/AI in beef cattle subjected to shortened-TAI protocols. In Expt. 1, nulliparous heifers were randomly assigned to a P4-releasing intravaginal device (PRID-Delta, 1.55 g P4) or a controlled internal drug release (CIDR, 1.38 g P4) at the initiation of a J-synch protocol. Heifers that displayed estrus 72 h following device removal were TAI, or if not in estrus given GnRH at 72 h and TAI at 90 h. In Expt. 2, nulliparous heifers and non-suckling cows were randomly assigned to either PRID or CIDR groups and either 1 or 2 mg of estradiol benzoate (EB) at initiation of a J-synch protocol. All cattle were TAI concurrent with GnRH 72 h after device removal. In Expt. 3, nulliparous heifers and suckling cows were randomly assigned to either PRID or CIDR groups and initiated a 5-d Cosynch protocol, with TAI concurrent with GnRH 72 h following device removal. In each experiment, cattle received estrus detection patches at device removal, which were then scored from 0 to 3 based on color change between initial application and TAI; 0 = unchanged, 1 = ≤50% change, 2 = >50% change, 3 = missing. Estrus was defined to have occurred when the patch was scored 2 or 3. Transrectal ultrasonography was used to determine cyclicity, diagnose pregnancy in all experiments, and the size of the ovulatory follicle in Expt. 3. In Expt. 1, the estrus rate was greater (72.0% vs. 61.0%; P = 0.04) in the PRID compared to the CIDR group. In Expt. 2, a parity by EB dose interaction (P = 0.02) was attributed to an increased estrus rate (52.8% vs. 41.4%; P = 0.05) in heifers given 1 vs. 2 mg EB. In Expt. 3, there was no difference in the ovulatory follicle diameter at device removal (P = 0.22) or TAI (P = 0.28) between P4 groups. Treatment with a PRID tended (P = 0.10) to increase the P/AI in cows compared to a CIDR (73.5% vs. 61.0%). In all experiments combined, the overall P/AI tended to increase (55.2% vs. 51.0%; P = 0.08) and P/AI in cattle exhibiting estrus increased (64.4% vs. 59.7%; P = 0.02) in cattle given a PRID compared to those given a CIDR, respectively. In summary, the type of intravaginal P4 device affected estrus response and P/AI following TAI in beef cows.