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Objective: Hearing decline in ageing increases the risk of loneliness and social isolation. This correlation is most often observed when hearing is measured by subjective self-report, and less often for objectively measured speech listening ability, raising questions about differences between self-assessments and behavioural performance. This study compared self-reported hearing ability and objective speech-in-noise performance as predictors of loneliness and social isolation in adults older than 60., Design: This was an observational, cross-sectional online study. Participants were instructed to complete a speech-in-noise task to measure objective listening ability, as well as four questionnaires that measured subjective self-rated hearing, feelings of loneliness, perceived social support, and depression and anxiety., Study Sample: One-hundred fifteen individuals aged above 60 with no treated hearing loss., Results: No correlation was found between loneliness scores and subjective self-rated hearing or objective speech-in-noise perception after adjusting demographic variables and overall psychological distress (anxiety and depression). However, self-rated hearing was positively correlated with social support when anxiety/depression scores were low. When anxiety/depression scores were high, this relationship was attenuated. Objective speech-in-noise perception did not correlate with perceived social support., Conclusions: Self-rated hearing ability positively predicts ratings of social support in older adults with low levels of psychological distress.

Introduction: Suicidal ideation and attempts are considered to be graduated risks for suicide, yet they remain under studied. Suicide is among the leading causes of death in the U.S. for all individuals between the ages of 10 and 64 years. Suicide is a critical problem in the U.S. Military. The U.S. Army suicide rates surpassed civilian rates in 2008 and continue to climb steadily; with U.S. Army soldiers at more than twice the risk than U.S. civilians, and enlisted personnel at more than twice the risk of officers. Suicidal ideation and attempts are routinely reported within U.S. Army brigades using suicide-related serious incident reports (SR-SIRs). These reports could form a useful source of information for prevention planning, but to date there have been no efforts to summary these reports. This paper analyzes SR-SIRs among enlisted personnel for a 4-year period for 1 Army brigade, to test the usefulness of this information and to explore whether risk factors for attempts compared to ideation can be identified., Materials and Methods: This report analyzes 130 de-identified reports of suicidal ideation (n = 102) and suicide attempts (n = 28) reported as SR-SIRs from August 2018 to June 2022 among enlisted personnel in an airborne infantry brigade combat team (BCT) outside the continental U.S. Analysis of de-identified data was not considered research by brigade and university human subject/IRB authorities. Fourteen soldier characteristics and context factors were examined to determine if they differentiate the two types of incidents, suicidal ideations and suicide attempts., Results: Unit location and alcohol use at the time of the incident were strongly associated with suicide attempts compared to ideation. Attempts occurred disproportionately during off duty hours, and attempters were more likely to have had prior contact with behavioral health services than ideators; however, these differences did not attain conventional statistical significance., Conclusions: The study can help inform unit-specific suicide prevention and intervention strategies. Off duty hours and alcohol use are risk factors for attempts, particularly among soldiers who have sought behavioral health care. Plans to engage and support soldiers who have sought behavioral health care during off duty hours, and information regarding the risks of alcohol use, could meaningfully reduce their risk. This is the first known attempt to examine active duty U.S. Army brigade combat team SR-SIRs, and they are a potentially valuable source of health and mental health-related information., (© The Association of Military Surgeons of the United States 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Diseases caused by small ruminant lentiviruses, Mycobacterium avium ssp. paratuberculosis (MAP), Schmallenberg virus, and peste des petits ruminants virus (PPR) is globally recognised as serious threats to the ruminant industry due to their potential to spread rapidly across boundaries. Despite their global distribution and negative impacts on ruminant production, there is a gap in knowledge of the current trends in their epidemiology among sheep and goat populations in Peninsular Malaysia. This study was therefore designed to fill the gap of knowledge concerning the seroprevalence and contributing factors of CAEV, paratuberculosis, SBV, and PPRV among small ruminants from selected flocks in Selangor, Negeri Sembilan, and Pahang states in Peninsular Malaysia. A cross-sectional study design was used to collect animal data and blood samples for serological assays simultaneously. The ID Screen (ID.VET, France) indirect ELISA screening tests were used to detect serum antibodies directed against CAEV/MVV (VISNAS Ver 0922), paratuberculosis (PARAS Ver 0516), SBV (SBVC Ver 1114) and PPRV (PPRC Ver 0821). There was 45.4% (95% CI = 40.74-50.74), 6.8% (95% CI = 4.66-9.69), 27.8% (95% CI = 23.35-32.77), and 2.6% (95% CI = 1.11-0.51) true seroprevalence for CAEV, paratuberculosis, SBV, and PPR, respectively. Geographical location and species were the risk factors for CAEV and paratuberculosis, while the management system and age of small ruminants were the risk factors for SBV. The present study is the first to document a large-scale seroprevalence of MAP and PPR infection among sheep and goat flocks in Peninsular Malaysia. The presence of PPRV and MAP antibodies among small ruminant flocks is signalling current or previous exposure to the pathogens or cross reactions with similar antigens. This finding further suggests the potential for future outbreaks of these devastating diseases among sheep and goats in Malaysia. The high seroprevalence of CAEV and SBV among small ruminants indicates high levels of exposure to the viruses in the environment, which is a potential threat to production., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

This paper describes the occurrence of multiple parasitic infection with special reference to emerging haemotropic Mycoplasma ovis. A cross-sectional survey of four selected goat flocks was conducted to collect samples and management information. Blood samples were processed using microhaematocrit centrifugation to determine the packed cell volume (PCV). Detection and morphological identification of blood protozoa and haemotropic Mycoplasma ovis from Giemsa-stained smears were done microscopically. M. ovis infection was classified mild (1-29% infected cells), moderate (30-59% infected cells), or severe (above 60% infected cells). Faecal floatation and McMaster faecal egg count were used to detect and classify strongyle infections as negative (no eggs/oocysts), light (< 500 epg), Moderate (500 - 1000 epg), or severe (>1000 epg) and coccidia infection as light (<1800 opg), moderate (1800 - 6000 opg), or severe (>6000 opg). There were 149 goats with blood protozoa (57.98%; 95% CI: 51.87 - 63.85) and 204 goats with GI parasites (79.38%; 95% CI: 74.02 - 83.87) involved in single (15.8%; 95% CI: 11.7 - 21.0) or multiple (84.2%; 95% CI: 79.0 - 88.3) infections. The risk of Strongyles increases by 2.49 (95% CI: 1.24 - 4.99) in females versus males and 6.79 (95% CI: 3.25 - 14.18, p =0.000) in adults versus young. The risk of Eimeria species increases by 7.32 (95% CI: 3.45 - 15.50, p =0.000) in adults versus young, while M. ovis coinfection risk increases by 4.51 (95% CI: 1.40 - 14.50, p =0.000) in female versus males. Thin animals had a significantly higher (p<0.05) mean burden of Strongyle (1370.37 ± 345.49) and Eimeria (1594.12 ± 695.26) than the moderate and fat goats. The PCV was negatively associated with mean faecal egg count (FEC) (p<0.05) such that a lower PCV was recorded in animals with a higher Strongyle epg output. A severe burden of M. ovis was accompanied by an increased nematode FEC and decreased haematocrit (p<0.05). Coinfections of Strongyles, or Eimeria species involving M. ovis were associated with a higher parasitaemia compared with single infections (p<0.05). This study highlights the importance of M. ovis and Strongyle or Eimeria species coinfections among goat flocks and provides valuable data for developing and implementing an integrated herd health management program for parasite control among low-input smallholder flocks.

The lipopolysaccharide (LPS) endotoxin and outer membrane protein (OMP) are among the virulence factors of Gram-negative bacteria responsible for inducing pathogenicity in the infected host. OMP and LPS occur on the outer membrane of M. haemolytica A2, the primary aetiological agent of pneumonic mannheimiosis in small ruminants. While the LPS is known to mediate Gram-negative bacterial infection by activating downstream inflammatory pathways, the potential role of OMP during inflammatory responses remained unclear. Hence, this study determined the effect of the OMP of M. haemolytica A2 on the serum concentration of pro-inflammatory cytokines and the male reproductive hormones (testosterone and Luteinizing Hormone). We randomly assigned twelve bucks to three groups (n = 4 bucks each): Group 1 was challenged with 2 mL PBS buffer (pH 7.0) intranasally; Group 2 received 2 mL of 1.2 X 10 9  CFU/mL whole M. haemolytica A2 intranasally; and Group 3 received 2 mL of OMP extract obtained from 1.2 X 10 9  CFU/mL M. haemolytica A2 intramuscularly. Serum samples collected at pre-determined intervals were used for the quantitative determination of the pro-inflammatory cytokines (IL-1β, IL-6, and TNFα) and reproductive hormones (testosterone and LH) using commercial sandwich enzyme-linked immunosorbent assay (ELISA). The serum concentration of IL1β was initially increased within the first-hour post-challenge in Groups 2 and 3, followed by a significant decrease in concentration at 21d and 35d (p < 0.05) in Group 3. Only mild fluctuations in IL-6 occurred in group 2, as opposed to the 1.7-fold rapid increase in TNFα within 2 h post-challenge before decreasing at 6 h. An increase in pro-inflammatory cytokines was accompanied by an acute febrile response of 39.5 ± 0.38 °C (p < 0.05) at 2 h and 40.1 ± 0.29 °C (p < 0.05) at 4 h in Group 2 and Group 3, respectively. Serum testosterone decreased significantly (p < 0.05) in both treatment groups but remained significantly (p > 0.05) lower than in Group 1 throughout the study. There was a moderate negative association between testosterone and IL1β (r = -0.473; p > 0.05) or TNFα (r = -0.527; p < 0.05) in Group 2. Serum LH also showed moderate negative associations with TNFα in Group 2 (r = -0.63; p < 0.05) and Group 3 (r = -0.54; p > 0.05). The results of this study demonstrated that M. haemolytica A2 and its OMP produced marked alterations in serum levels of pro-inflammatory cytokines and male reproductive hormones. The negative correlations between serum testosterone and inflammatory cytokines would suggest the potential role of OMP in causing male infertility by mediating innate inflammatory responses to suppress testosterone production in bucks., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

DNA damaging agents are a mainstay of standard chemotherapy for ovarian cancer. Unfortunately, resistance to such DNA damaging agents frequently develops, often due to increased activity of DNA repair pathways. Sideroflexin 4 (SFXN4) is a little-studied inner mitochondrial membrane protein. Here we demonstrate that SFXN4 plays a role in synthesis of iron sulfur clusters (Fe-S) in ovarian cancer cells and ovarian cancer tumor-initiating cells, and that knockdown of SFXN4 inhibits Fe-S biogenesis in ovarian cancer cells. We demonstrate that this has two important consequences that may be useful in anti-cancer therapy. First, inhibition of Fe-S biogenesis triggers the accumulation of excess iron, leading to oxidative stress. Second, because enzymes critical to multiple DNA repair pathways require Fe-S clusters for their function, DNA repair enzymes and DNA repair itself are inhibited by reduction of SFXN4. Through this dual mechanism, SFXN4 inhibition heightens ovarian cancer cell sensitivity to DNA-damaging drugs and DNA repair inhibitors used in ovarian cancer therapy, such as cisplatin and PARP inhibitors. Sensitization is achieved even in drug resistant ovarian cancer cells. Further, knockout of SFXN4 decreases DNA repair and profoundly inhibits tumor growth in a mouse model of ovarian cancer metastasis. Collectively, these results suggest that SFXN4 may represent a new target in ovarian cancer therapy., (© 2022. The Author(s).)

There is a weak relationship between clinical and self-reported speech perception outcomes in cochlear implant (CI) listeners. Such poor correspondence may be due to differences in clinical and "real-world" listening environments and stimuli. Speech in the real world is often accompanied by visual cues, background environmental noise, and is generally in a conversational context, all factors that could affect listening demand. Thus, our objectives were to determine if brain responses to naturalistic speech could index speech perception and listening demand in CI users. Accordingly, we recorded high-density electroencephalogram (EEG) while CI users listened/watched a naturalistic stimulus (i.e., the television show, "The Office"). We used continuous EEG to quantify "speech neural tracking" (i.e., TRFs, temporal response functions) to the show's soundtrack and 8-12 Hz (alpha) brain rhythms commonly related to listening effort. Background noise at three different signal-to-noise ratios (SNRs), +5, +10, and +15 dB were presented to vary the difficulty of following the television show, mimicking a natural noisy environment. The task also included an audio-only (no video) condition. After each condition, participants subjectively rated listening demand and the degree of words and conversations they felt they understood. Fifteen CI users reported progressively higher degrees of listening demand and less words and conversation with increasing background noise. Listening demand and conversation understanding in the audio-only condition was comparable to that of the highest noise condition (+5 dB). Increasing background noise affected speech neural tracking at a group level, in addition to eliciting strong individual differences. Mixed effect modeling showed that listening demand and conversation understanding were correlated to early cortical speech tracking, such that high demand and low conversation understanding occurred with lower amplitude TRFs. In the high noise condition, greater listening demand was negatively correlated to parietal alpha power, where higher demand was related to lower alpha power. No significant correlations were observed between TRF/alpha and clinical speech perception scores. These results are similar to previous findings showing little relationship between clinical speech perception and quality-of-life in CI users. However, physiological responses to complex natural speech may provide an objective measure of aspects of quality-of-life measures like self-perceived listening demand., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xiu, Paul, Chen, Le, Lin and Dimitrijevic.)

Deaf individuals who use a cochlear implant (CI) have remarkably different outcomes for auditory speech communication ability. One factor assumed to affect CI outcomes is visual crossmodal plasticity in auditory cortex, where deprived auditory regions begin to support non-auditory functions such as vision. Previous research has viewed crossmodal plasticity as harmful for speech outcomes for CI users if it interferes with sound processing, while others have demonstrated that plasticity related to visual language may be beneficial for speech recovery. To clarify, we used electroencephalography (EEG) to measure brain responses to a partial face speaking a silent single-syllable word (visual language) in 15 CI users and 13 age-matched typical-hearing controls. We used source analysis on EEG activity to measure crossmodal visual responses in auditory cortex and then compared them to CI users' speech-in-noise listening ability. CI users' brain response to the onset of the video stimulus (face) was larger than controls in left auditory cortex, consistent with crossmodal activation after deafness. CI users also produced a mixture of alpha (8-12 Hz) synchronization and desynchronization in auditory cortex while watching lip movement while controls instead showed desynchronization. CI users with higher speech scores had stronger crossmodal responses in auditory cortex to the onset of the video, but those with lower speech scores had increases in alpha power during lip movement in auditory areas. Therefore, evidence of crossmodal reorganization in CI users does not necessarily predict poor speech outcomes, and differences in crossmodal activation during lip reading may instead relate to strategies or differences that CI users use in audiovisual speech communication., (© 2022. The Author(s).)

Pneumonic mannheimiosis is a widespread respiratory bacterial disease of small ruminants caused by Mannheimia haemolytica serotype A2. The disease is known to affect the respiratory organs of infected animals, but its effect on other vital and reproductive organs has not been fully explored. Previous studies have demonstrated increased serum pro-inflammatory cytokine concentration post-challenge with M. haemolytica A2 and its LPS, indicating systemic inflammation in the host. This study determined the potential tissue changes and alterations of sperm parameters due to infection of M. haemolytica A2 and its LPS endotoxin. In this study, twelve experimental bucks were randomly assigned to three groups of four bucks each: group 1 (control group) were intranasally inoculated with 2 mL of PBS pH 7.0, group 2 received 2 mL of 1.2 × 10 9  CFU/mL M. haemolytica A2 intranasally, and group 3 received 2 mL of LPS extracted from 1.2 × 10 9  CFU/mL of M. haemolytica A2 intravenously. Semen samples were collected at pre-determined intervals using an electro-ejaculator and analysed immediately after collection. All experimental bucks were slaughtered via exsanguination on day 60 to collect their vital and reproductive organs at necropsy, and the samples were processed and analysed for histopathological changes. The current study has revealed that bucks challenged with M. haemolytica A2 and its LPS exhibited alterations in semen parameters such as motility, wave pattern, viability, and morphological abnormalities. Mild to moderate histopathological changes of the lung, liver, testis, epididymis, vas deferens, prostate, and lymph nodes were also observed in both challenged groups. Therefore, this study revealed the potential harmful effects of respiratory mannheimiosis on the reproductive organs of the infected bucks and sheds light on the expanse of systemic effects of this disease., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Mannheimia haemolytica causative agent of pneumonic mannheimiosis, a common respiratory disease of goat and sheep, which cause huge economic losses to farmers worldwide. Pneumonic mannheimiosis caused by M. haemolytica serotype A2 has been reported among small ruminants in Malaysia. The lipopolysaccharide (LPS) and outer membrane protein (OMP) are major virulence determinants for M. haemolytica serotype A2. Although pneumonic mannheimiosis is known to cause poor reproductive performance in small ruminants under field conditions, there is a dearth of published information on the specific effects of M. haemolytica serotype A2 infection on the female reproductive physiology. In this experiment, we explored the impact of M. haemolytica serotype A2 and its OMP immunogen on selected pro-inflammatory cytokines, acute phase proteins, female reproductive hormones, and cellular changes in visceral and female reproductive organs of non-pregnant does., Methodology: Twelve healthy, non-pregnant, Boer crossbreds does were divided equally into three groups (n = 4); Group 1 served as the negative control and was challenged with 2 ml of sterile PBS intranasally. Group 2 served as the positive control and was challenged with 2 ml of 10 9 colonies forming unit (CFU) of M. haemolytica serotype A2 suspension intranasally. Group 3 was challenged with 2 ml of OMP extracted from 10 9  CFU of M. haemolytica A2 intramuscularly. The experimental does were monitored for clinical signs and responses periodically. Blood samples were collected at 0, 1, 2, 4, 6, 12 and 24 h and 3, 7, 21, 35 and 56 days post treatment for serological analyses. All does were euthanised using the halal slaughter method on day 60 post challenge/treatment. Tissues from the uterus, liver, lung and associated bronchial lymph nodes were collected and fixed in 10% formalin for 14 days for histopathological study., Results: Compared to the control group, the challenged/treated groups showed significant (p < 0.05) increase in the rectal temperature, respiratory rate, heart rate, and rumen motility. Serum analyses revealed that the concentrations of progesterone and estrogen hormones were significantly (p < 0.05) decreased in groups 2 & 3. In contrast, the concentrations of pro-inflammatory cytokines (IL-1β and IL-6) and acute phase proteins (Hp and SAA) were significantly increased (p < 0.05) in the challenged/treated groups compared to the control group. Histopathological lesion scoring revealed mild to moderate cellular changes characterised by congestion, haemorrhage, degeneration, leucocytic cellular infiltration, and cellular necrosis in the tissues of does from the OMP treatment and bacterial challenge groups compared to the control group., Conclusion: The findings from this study suggests that M. haemolytica serotype A2 and its OMP immunogen induced mild to moderate inflammatory and degenerative changes which may potentially interfere with fertilization through hormonal imbalances and cause temporary loss of fertility in infected does., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Previous investigations have revealed that lipopolysaccharide (LPS) endotoxin from certain Gram-negative bacteria could adversely affect the reproductive system of female animals. However, it is unknown whether LPS endotoxin of Mannheimia haemolytica serotype A2, the principal causative bacteria that cause pneumonic mannheimiosis in small ruminants, may also induce similar insidious effects. Therefore, this study aimed to investigate the effects of M. haemolytica serotype A2 and its LPS endotoxin on the responses of female gonadal hormones (progesterone and oestrogen), pro-inflammatory cytokines (interleukin-1β, interleukin-6), acute-phase proteins (haptoglobin and serum amyloid A) and cellular changes via histopathology study of female reproductive organs of the treatment does. Twelve clinically healthy, non-pregnant, crossbred does were randomly allocated into three equal groups. Group 1 was administered intranasally with 2 ml of sterile phosphate-buffered saline (PBS) and served as a negative control group. Group 2 was challenged intranasally with 2 ml of bacterial inoculum containing 10 9 colony-forming units (CFU)/ml of M. haemolytica serotype A2, while Group 3 was challenged intravenously with 2 ml of LPS endotoxin extracted from 10 9  CFU/ml of M. haemolytica serotype A2. Following that, blood samples were collected serially at pre-determined intervals for serological analyses. All does were euthanised 60 days post-challenges, and tissue samples from the ovaries, oviducts, uterine horns, uterine body, cervix and vagina were collected for histopathological study. The serological result revealed a significant increase (p < 0.05) in the mean concentrations of progesterone, oestrogen, interleukin-1β, interleukin-6, haptoglobin and serum amyloid A for both challenged groups. Histopathologically, all reproductive organs (except the cervix and vagina) from both challenged groups displayed significant cellular alterations (p < 0.05) characterised by haemorrhage and congestion, necrosis and degeneration, inflammatory cell infiltration and oedema. This study provides new information that elucidates the potential role of pneumonic mannheimiosis in the pathogenesis of female infertility amongst small ruminants., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Moderate noise exposure may cause acute loss of cochlear synapses without affecting the cochlear hair cells and hearing threshold; thus, it remains "hidden" to standard clinical tests. This cochlear synaptopathy is one of the main pathologies of noise-induced hearing loss (NIHL). There is no effective treatment for NIHL, mainly because of the lack of a proper drug-delivery technique. We hypothesized that local magnetic delivery of gene therapy into the inner ear could be beneficial for NIHL. In this study, we used superparamagnetic iron oxide nanoparticles (SPIONs) and a recombinant adeno-associated virus (AAV) vector (AAV2(quad Y-F)) to deliver brain-derived neurotrophic factor (BDNF) gene therapy into the rat inner ear via minimally invasive magnetic targeting. We found that the magnetic targeting effectively accumulates and distributes the SPION-tagged AAV2(quad Y-F)-BDNF vector into the inner ear. We also found that AAV2(quad Y-F) efficiently transfects cochlear hair cells and enhances BDNF gene expression. Enhanced BDNF gene expression substantially recovers noise-induced BDNF gene downregulation, auditory brainstem response (ABR) wave I amplitude reduction, and synapse loss. These results suggest that magnetic targeting of AAV2(quad Y-F)-mediated BDNF gene therapy could reverse cochlear synaptopathy after NIHL., (Copyright © 2021 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)