bluuebunny/crossref_metadata_2025 huggingface dataset:
Pastoral practices, pressures, and human-wildlife relations in high altitude rangelands of eastern Himalaya: A case study of the Dokpa pastoralists of North Sikkim
Authors: Luxom Nisam Mang , Singh Rashmi , Theengh Laktsheden , Shrestha Priyadarshinee , Sharma Rishi Kumar
Published: September 2022

The pastoral practices of the Dokpa herders of North Sikkim have been transforming in response to the geo-political and socio-economic changes in the region. Against the backdrop of these changes, this study aims to understand the current state of pastoralism in North Sikkim with three specific objectives: (i) to understand the current rangeland management practices of the Dokpa community; (ii) to examine the social, political and ecological stresses to continuity of traditional pastoral livelihoods; and (iii) to document the baseline on human-wildlife relations. We focused on one of the two subset populations of Dokpa herders of North Sikkim and, using a mixed-methods approach, conducted 12 semi-structured interviews, four key respondent interviews and two focused group discussions. The resource use by the Dokpas is unique, and unlike the rest of the Himalayan range, they access the high-altitude pastures in winters and the lower ones in summer. Pastures in the higher altitudes experience heavier winds, which leads to lower levels of snow deposition — thus ensuring access to dried pasture forage for livestock during the lean season. The decisions pertaining to resource management are taken by the head of the local institution Dzumsa, the Pipon. Primary stresses to the continuation of traditional pastoral practices are fragmentation of pastureland post-Sino-Indian war of 1962 and the consequent establishment of armed forces, livestock depredation by free-ranging dogs followed by wild predators and continued socio-economic marginalisation of the pastoralists under a supposedly egalitarian institutional regime. Extreme climatic events in the recent past have also contributed to significant livestock loss. Dokpa transhumant practices are on an overall decline, with most members of the younger generation shifting to non-herding livelihoods. The availability of alternate livelihood options with the improved connectivity, access to education and development of the tourism industry has led to changing aspirations of the younger generations. In only two of the twelve households we surveyed, the younger generation continues herding, while the rest have moved to the cities and towns. In terms of human-wildlife relations, the respondents mostly hold a positive attitude towards wildlife and conservation actions despite livestock predation by wild predators, since the free-ranging dogs cause the highest livestock loss. With the inputs from the Dokpas, we provide recommendations towards a facilitative environment for the continuation of the traditional herding in the region, which is critical for the survival of pastoralism in North Sikkim, presently hinged on less than two dozen of elderly Dokpas.
The therapeutic prospects and challenges of human neural stem cells for the treatment of Alzheimer's Disease
Authors: Yue Chunmei , Feng Su , Chen Yingying , Jing Naihe
Published: September 2022

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder associated with aging. Due to its insidious onset, protracted progression, and unclear pathogenesis, it is considered one of the most obscure and intractable brain disorders, and currently, there are no effective therapies for it. Convincing evidence indicates that the irreversible decline of cognitive abilities in patients coincides with the deterioration and degeneration of neurons and synapses in the AD brain. Human neural stem cells (NSCs) hold the potential to functionally replace lost neurons, reinforce impaired synaptic networks, and repair the damaged AD brain. They have therefore received extensive attention as a possible source of donor cells for cellular replacement therapies for AD. Here, we review the progress in NSC-based transplantation studies in animal models of AD and assess the therapeutic advantages and challenges of human NSCs as donor cells. We then formulate a promising transplantation approach for the treatment of human AD, which would help to explore the disease-modifying cellular therapeutic strategy for the treatment of human AD.
Aldehyde dehydrogenase 2 rs671 polymorphism and multiple diseases: protocol for a quantitative umbrella review of meta-analyses
Authors: He Zhengting , Guo Qi , Ling Yikai , Hong Chuan , Liu Yuqing , Jin Xurui , Thanaporn Porama , Zhao Duan , Wang Leiting , Liu Liang , Yan Lijing L.
Published: September 2022

Background

The mutant allele (*2) of aldehyde dehydrogenase type 2 (ALDH2) caused by a single nucleotide variant (rs671) inhibits enzymatic activity and is associated with multiple diseases. In recent years, an explosive number of original studies and meta-analyses have been conducted to examine the associations of ALDH2 rs671 polymorphism with diseases. Due to conflicting results, the overall associations of ALDH2 rs671 polymorphism and multiple diseases remain unclear.

Methods

A quantitative umbrella review will be conducted on meta-analyses of genetic association studies to examine the pleiotropic effects of ALDH2 rs671, mainly including cardio-cerebral vascular disease, diabetes mellitus, cancer, neurodegenerative disease, and alcohol-induced medical disease. A search of relevant literature according to comprehensive search strategies will be performed on studies published before July 1st, 2022 in PubMed, MEDLINE Ovid, Embase, Cochrane Database of Systematic Reviews, and Web of Science. Study selection, data extraction, methodology quality assessment, and strength of evidence assessment will be conducted by two reviewers independently and in duplicate. Included meta-analyses will be grouped by outcomes. Data conflicts and overlap between meta-analyses will be managed through updated standardized and customized methods including the calculation of CCA for study selection reference, application of Doi plots to assess small-study effects and others. Evidence from included meta-analyses will be quantitatively synthesized by overlap-corrected analyses and meta-analysis using primary studies.

Discussion

This umbrella review is expected to generate systematic evidence on the association between ALDH2 rs671 and diseases. Specific approaches were developed to address key challenges in conducting an umbrella review, including assessment tools of methodology and evidence quality of meta-analyses, methods to manage overlap between meta-analyses, a “stop-light” plot to summarize key findings. These approaches provide applicable methods for future umbrella reviews of meta-analyses on genetic association studies.

Trial registration

CRD42021223812
Duration of immunity following full vaccination against SARS-CoV-2: a systematic review
Authors: Addo Isaac Yeboah , Dadzie Frederick Asankom , Okeke Sylvester Reuben , Boadi Caleb , Boadu Elijah Frimpong
Published: September 2022

Background

As vaccine roll-out continues across the globe as part of the efforts to protect humanity against SARS-CoV-2, concerns are increasingly shifting to the duration of vaccine-induced immunity. Responses to these concerns are critical in determining if, when, and who will need booster doses following full vaccination against SARS-CoV-2. However, synthesised studies about the durability of vaccine-induced immunity against SARS-CoV-2 are scarce. This systematic review synthesised available global evidence on the duration of immunity following full vaccination against SARS-CoV-2.

Methods

We searched through Psych Info, Web of Science, Scopus, Google Scholar, PubMed, and WHO COVID-19 databases for relevant studies published before December 2021. Five eligibility criteria were used in scrutinising studies for inclusion. The quality of the included studies was assessed based on Joana Briggs Institute’s (JBI) Critical Appraisal tool and Cochrane’s Risk of Bias tool—version 2 (RoB 2), while the reporting of the results was guided by the Synthesis Without Meta-analysis (SWiM) guidelines.

Results

Twenty-seven out of the 666 identified studies met the inclusion criteria. The findings showed that vaccine-induced protection against SARS-CoV-2 infections builds rapidly after the first dose of vaccines and peaks within 4 to 42 days after the second dose, before waning begins in subsequent months, typically from 3 to 24 weeks. Vaccine-induced antibody response levels varied across different demographic and population characteristics and were higher in people who reported no underlying health conditions compared to those with immunosuppressed conditions.

Conclusions

Waning of immunity against SARS-CoV-2 begins as early as the first month after full vaccination and this decline continues till the sixth month when the level of immunity may not be able to provide adequate protection against SARS-CoV-2. While the evidence synthesised in this review could effectively inform and shape vaccine policies regarding the administration of booster doses, more evidence, especially clinical trials, are still needed to ascertain, with greater precision, the exact duration of immunity offered by different vaccine types, across diverse population characteristics, and in different vulnerability parameters.

Registration

The protocol for this review was pre-registered with the International Prospective Register of Systematic Reviews [PROSPERO] (Registration ID: CRD420212818).
Characterization of ACE2 naturally occurring missense variants: impact on subcellular localization and trafficking
Authors: Badawi Sally , Mohamed Feda E. , Alkhofash Nesreen R. , John Anne , Ali Amanat , Ali Bassam R.
Published: September 2022

Background

Human angiotensin-converting enzyme 2 (ACE2), a type I transmembrane receptor physiologically acting as a carboxypeptidase enzyme within the renin-angiotensin system (RAS), is a critical mediator of infection by several severe acute respiratory syndrome (SARS) corona viruses. For instance, it has been demonstrated that ACE2 is the primary receptor for the SARS-CoV-2 entry to many human cells through binding to the viral spike S protein. Consequently, genetic variability in ACE2 gene has been suggested to contribute to the variable clinical manifestations in COVID-19. Many of those genetic variations result in missense variants within the amino acid sequence of ACE2. The potential effects of those variations on binding to the spike protein have been speculated and, in some cases, demonstrated experimentally. However, their effects on ACE2 protein folding, trafficking and subcellular targeting have not been established.

Results

In this study we aimed to examine the potential effects of 28 missense variants (V801G, D785N, R768W, I753T, L731F, L731I, I727V, N720D, R710H, R708W, S692P, E668K, V658I, N638S, A627V, F592L, G575V, A501T, I468V, M383I, G173S, N159S, N149S, D38E, N33D, K26R, I21T, and S19P) distributed across the ACE2 receptor domains on its subcellular trafficking and targeting through combinatorial approach involving in silico analysis and experimental subcellular localization analysis. Our data show that none of the studied missense variants (including 3 variants predicted to be deleterious R768W, G575V, and G173S) has a significant effect on ACE2 intracellular trafficking and subcellular targeting to the plasma membrane.

Conclusion

Although the selected missense variants display no significant change in ACE2 trafficking and subcellular localization, this does not rule out their effect on viral susceptibility and severity. Further studies are required to investigate the effect of ACE2 variants on its expression, binding, and internalization which might explain the variable clinical manifestations associated with the infection.
“The male elephant in the room”: a qualitative evidence synthesis exploring male experiences of eating disorders
Authors: Coopey Emily , Johnson George
Published: September 2022

Background

Men are believed to be underrepresented in eating disorder services; there are many reasons presented to account for this such as a lack of recognition and detection. Due to the physical and psychological complexity of an eating disorder it is important to understand this underrepresentation. This qualitative evidence synthesis aimed to explore the literature relating to men’s experiences of an eating disorder, in order to synthesise the findings and offer a more coherent understanding.

Method

A systematic search of the literature was undertaken. Inclusion and exclusion criteria were applied to the findings resulting in 14 papers deemed suitable for inclusion. A Meta-Ethnographic approach to synthesising the data of the 89 participants was undertaken.

Results

Four themes were identified: ‘Societal Construction of the Perfect Male’; ‘Striving to Maintain a Masculine Identity’; ‘The Interconnectedness of Control and Self-Worth’, and ‘The Hidden Man’. There appeared to be an underlying concept relating to the conflict of being a man, with what is perceived to be a ‘woman’s illness’ and how this challenged the men’s experiences of masculinity.

Conclusions

Being a man with an eating disorder conflicted with societal norms, exacerbating their experience of having an eating disorder.. To resolve this, gendered norms need to shift, at societal level as well as considering how best to improve understanding and recognition of men with an eating disorder at the first point of help seeking.
Fatal disseminated mucormycosis due to Cunninghamella bertholletiae infection after ABO-incompatible living donor liver transplantation: a case report
Authors: Mita Atsuyoshi , Hirano Shohei , Uehara Takeshi , Uehara Kai , Ohno Yasunari , Kubota Koji , Masuda Yuichi , Notake Tsuyoshi , Yoshizawa Kazuki , Shimizu Akira , Soejima Yuji
Published: September 2022

Background

Fungal infection may develop because of immunosuppression after organ transplantation, in which invasive types, such as Aspergillus and Mucorales, fungi cause morbidity. We present a case of disseminated mucormycosis due to Cunninghamella bertholletiae after ABO-incompatible living donor liver transplantation (LDLT).

Case presentation

A 47-year-old man with decompensated liver cirrhosis and hepatocellular carcinoma underwent an ABO-incompatible LDLT using a graft procured from his son, who had a different blood type. Rituximab and mycophenolate mofetil were administered 3 weeks before LDLT as immunosuppressive therapy. Although liver graft function improved, mass-like infiltrates appeared in the lungs following intubation for > 1 week due to impaired consciousness. The brain magnetic resonance imaging findings were normal. Decreased ejection fraction and ST elevation were detected on echocardiography and electrocardiography, respectively. There was no dominant stenosis on coronary arteriography. The recipient underwent segmentectomy of the right lung 20 days after LDLT. C. bertholletiae was identified from a specimen using polymerase chain reaction, thus establishing a diagnosis of mucormycosis. Multiple infarctions in the brain, heart, and kidney developed within 2 weeks. Treatment with amphotericin B was ineffective. The patient developed circulatory collapse, and a temporary pacemaker and percutaneous coronary intervention were required for cardiac infarction. The recipient died of cardiac failure 27 days after the LDLT. Autopsy revealed disseminated mucormycosis involving the brain, thyroid, heart, lung, liver, gastrointestinal tract, and both kidneys. In addition, fungal endocarditis may have been responsible for septic emboli in multiple organs, resulting in multiple organ invasion. Hypothrombocytopenia was present since the pre-transplant period, and the recipient was diagnosed posthumously with myelodysplastic syndrome due to hereditary abnormalities. Multiple factors such as organ transplantation, bone marrow dysfunction, immunosuppression, and inadequate administration of antifungal reagents might have promoted mucormycosis development in our patient.

Conclusions

Mucormycosis by C. bertholletiae is a fatal complication; thus, early diagnosis and treatment are warranted before multiple organ invasion.
Hospitalized for poverty: orthopaedic discharge delays due to financial hardship in a tertiary hospital in Northern Tanzania
Authors: Obayemi Joy E. , Card Elizabeth B. , Shirima Octavian , Premkumar Ajay , Massawe Honest , Sheth Neil P.
Published: September 2022

Background

Musculoskeletal injury contributes significantly to the burden of disease in Tanzania and other LMICs. For hospitals to cope financially with this burden, they often mandate that patients pay their entire hospital bill before leaving the hospital. This creates a phenomenon of patients who remain hospitalized solely due to financial hardship. This study aims to characterize the impact of this policy on patients and hospital systems in resource-limited settings.

Methods

A mixed-methods study using retrospective medical record review and semi-structured interviews was conducted at a tertiary hospital in Moshi, Tanzania. Information regarding patient demographics, injury type, days spent in the ward after medical clearance for discharge, and hospital invoices were collected and analyzed for orthopaedic patients treated from November 2016 to June 2017.

Results

346 of the 867 orthopaedic patients (39.9%) treated during this time period were found to have spent additional days in the hospital due to their inability to pay their hospital bill. Of these patients, 72 patient charts were analyzed. These 72 patients spent an average of 9 additional days in the hospital due to financial hardship (range: 1–64 days; interquartile range: 2–10.5 days). They spent an average of 112,958 Tanzanian Shillings (TSH) to pay for services received following medical clearance for discharge, representing 12.3% of the average total bill (916,840 TSH). 646 hospital bed-days were spent on these 72 patients when they no longer clinically required hospitalization. 7 (9.7%) patients eloped from the hospital without paying and 24 (33.3%) received financial assistance from the hospital’s social welfare office.

Conclusions

Many patients do not have the financial capacity to pay hospital fees prior to discharge. This reality has added significantly to these patients’ overall financial hardship and has taken hundreds of bed-days from other critically ill patients. This single-institution, cross-sectional study provides a deeper understanding of this phenomenon and highlights the need for changes in the healthcare payment structure in Tanzania and other comparable settings.
Paprikash (‘Paprykarz szczeciński’): transformation of maritime identities and domestication of ethnic food
Authors: Kowalewski Maciej , Bartłomiejski Robert
Published: September 2022

At the center of our research is the 'Paprykarz' (Paprikash—fish and rice sandwichpate), local fish food which is an example of the relations and networks in a field of maritime culture. These relations address both the question of the social memory of national fishing industry and a regional identity. Sold originally in a tin, ‘Paprykarz’ was an export hit in the 1980s, In fact, it was a domesticated version of a Senegalese dish, calledTiep bou dienn Sénégalais,Thieboudienne, The story of paprikash is an unusually interesting one for those researching ethnic food, due to the complexity of its case. The many intersecting narratives about paprikash include stories from the food and fisheries industries; stories of political transformation, domestication, Soviet colonialism, and Creolisation; stories, too, about creating local identity, about nutritional habits, and the idea ofslow food.
Traditional Brazilian fermented foods: cultural and technological aspects
Authors: Lima Thamylles Thuany Mayrink , Hosken Bianca de Oliveira , Venturim Bárbara Côgo , Lopes Isabelle Lima , Martin José Guilherme Prado
Published: September 2022

Fermented foods production started thousands of years ago and comprised a wide variety of products from different cultures and countries. The discovery of fermented foods is considered an empirical process based on human observation and experimentation of food types susceptible to natural biochemical and microbiological effects. Given the historical miscegenation of Brazilian people, the country has rich cultural diversity and a complex mix of ethnicities, religions and culinary traditions, among others. Thus, the current review aims at presenting the main cultural, microbiological and technological aspects of different types of fermented foods and beverages produced and consumed in Brazil, such as traditional artisanal cheeses, fermented meat (socolandcharqui), non-alcoholic or low-alcohol beverages (aluá, calugi, tarubáandyakupá), alcoholic beverages (cachaça, tiquira, caiçuma, cauimandcaxiri) and fermented foods based on cassava (puba, farinha d'água, polvilho azedoandtucupi).
The vertebrate- and testis- specific transmembrane protein C11ORF94 plays a critical role in sperm-oocyte membrane binding
Authors: Hao Hongying , Shi Baolu , Zhang Jiacheng , Dai Ao , Li Wenhao , Chen Haidi , Ji Wenya , Gong Chenjia , Zhang Chang , Li Jing , Chen Li , Yao Bin , Hu Peng , Yang Hao , Brosius Juergen , Lai Shanshan , Shi Qinghua , Deng Cheng
Published: September 2022

Sperm-oocyte membrane fusion is necessary for mammalian fertilization. The factors that determine the fusion of sperm with oocytes are largely unknown. So far, spermatozoon factor IZUMO1 and the IZUMO1 counter-receptor JUNO on the oocyte membrane has been identified as a protein requiring fusion. Some sperm membrane proteins such as FIMP, SPACA6 and TEME95, have been proved not to directly regulate fusion, but their knockout will affect the fusion process of sperm and oocytes. Here, we identified a novel gene C11orf94 encoding a testicular-specific small transmembrane protein that emerges in vertebrates likely acquired via horizontal gene transfer from bacteria and plays an indispensable role in sperm-oocyte binding. We demonstrated that the deletion of C11orf94 dramatically decreased male fertility in mice. Sperm from C11orf94-deficient mice could pass through the zona pellucida, but failed to bind to the oocyte membrane, thus accumulating in the perivitelline space. In consistence, when the sperm of C11orf94-deficient mice were microinjected into the oocyte cytoplasm, fertilized oocytes were obtained and developed normally to blastocysts. Proteomics analysis revealed that C11orf94 influenced the expression of multiple gene products known to be indispensable for sperm-oocyte binding and fusion, including IZUMO1, EQTN and CRISP1. Thus, our study indicated that C11ORF94 is a vertebrate- and testis-specific small transmembrane protein that plays a critical role in sperm binding to the oolemma.
A review on interventions for psychogenic nonepileptic seizures: which treatments improve outcome?
Authors: Simas J. , Nombora O. , Rio C.
Published: September 2022

Introduction

Psychogenic nonepileptic seizures (PNES), the most common conversion disorder, are episodic alterations in behaviour that resemble epileptic seizures without its characteristic EEG changes. PNES presumably reflect a physical manifestation of underlying psychological distress and can be as disabling as epilepsy. Standardized treatment approaches for PNES care are lacking.

Objectives

Our aim is to review the literature for therapeutic interventions in PNES.

Methods

A literature search was conducted in PubMed/MEDLINE database for randomized controlled trials (RCTs) examining the effect(s) of specific intervention(s) in patients with PNES. Search terms were “psychogenic-nonepileptic-seizures” and selection was based on the abstracts of all the studies retrieved. Priority outcome was frequency of PNES.

Results

We identified 8 eligible RCTs. Samples ranged from 19 to 82 patients. Follow-up periods varied from 6 weeks to 18 months. Regarding reduction of PNES frequency, several interventions were effective: motivational interviewing combined with psychotherapy; cognitive behavioural therapy informed psychotherapy (CBT-ip); combination of CBT-ip and sertraline; immediate withdrawal of antiepileptic drugs after PNES diagnosis; a standardized diagnostic approach associated with psychiatric inpatient consultation. Treatment with sertraline alone and brief educational interventions didn’t reduce PNES frequency significantly. Beside PNES rate reduction, most interventions conveyed some type of benefit such as improvement in quality of life, mood or functionality.

Conclusions

The majority of the beneficial interventions included a structured communicational approach and/or psychotherapeutic treatment. Our analysis highlights the importance of a multidisciplinary strategy that includes psychotherapy. Further studies with larger samples and longer follow-up periods are needed to robustly inform evidence-based treatment for PNES.

Disclosure

No significant relationships.
Body Image disturbance in patients with cancer
Authors: Guermazi A. , Hentati S. , Guermazi F. , Masmoudi R. , Baati I. , Feki I. , Masmoudi J.
Published: September 2022

Introduction

Cancer and its treatments have been shown to have a negative psychological effect on many cancer patients. One of these effects is often described as body image disturbance.

Objectives

To assess body image in cancer patients and its association with clinical variables.

Methods

This was a cross-sectional study, conducted over 1 month, involving 100 cancer patients followed in the oncology department at the Habib Bourguiba University Hospital in Sfax (Tunisia). All participants completed a 10-item Body Image Scale (BIS) questionnaire to assess body image dissatisfaction.

Results

These results showed that half of the patients were female, and 70% of them were married. Their mean age was 51.96 years with extremes ranging from 41 to 60 years. Their level of education did not exceed primary school in 61% of cases, and 68% of them were unemployed. A total of 58% of patients received chemotherapy and 44%, 25%, and 11% of persons were affected by breast, digestive and cavum cancer, respectively. Impaired body image was noted in 81% of cases with an average BIS score of 15.39. An altered body image was statistically correlated with female sex (p = 0.005), absence of professional activity (p = 0.032), and the presence of anxiety-depressive symptoms (p = 0.008).

Conclusions

In this study most of the cancer patients had body image disturbances. Therefore, it is to the health team and nurses that take the concept of body image more serious and make use of some interventions to minimize the possible side effects.

Disclosure

No significant relationships.
Gray Matter Deficits of Cortical-striatal-limbic Circuit in Social Anxiety Disorder
Authors: Zhang X. , Wang S. , Gong Q.
Published: September 2022

Introduction

The extant findings have been of great heterogeneity due to partial volume effects in the investigation of cortical gray matter volume (GMV), high comorbidity with other psychiatric disorders, and concomitant therapy in the neuroimaging studies of social anxiety disorder (SAD).

Objectives

To identity gray matter deficits in cortical and subcortical structures in non-comorbid never-treated patients, so as to explore the “pure” SAD-specific pathophysiology and neurobiology.

Methods

Thirty-two non-comorbid free-of-treatment patients with SAD and 32 demography-matched healthy controls were recruited to undergo high-resolution 3.0-Tesla T1-weighted MRI. Cortical thickness (CT) and subcortical GMV were estimated using FreeSurfer; then the whole-brain vertex-wise analysis was performed to compare group differences in CT. Besides, differences in subcortical GMV of priori selected regions-of-interest: amygdala, hippocampus, putamen, and pallidum were compared by an analysis of covariance with age, gender, and total subcortical GMV as covariates.

Results

The SAD patients demonstrated significantly decreased CT near-symmetrically in the bilateral prefrontal cortex (Monte Carlo simulations of P < 0.05). Besides, smaller GMV in the left hippocampus and pallidum were also observed in the SAD cohort (two-sample t-test of P < 0.05).

Conclusions

For the first time, the current study investigated the structural alterations of CT and subcortical GMV in non-comorbid never-treated patients with SAD. Our findings provide preliminary evidences that structural deficits in cortical-striatal-limbic circuit may contribute to the psychopathological basis of SAD, and offer more detailed structural substrates for the involvement of such aberrant circuit in the imbalance between defective bottom-up response and top-down control to external stimuli in SAD.

Disclosure

No significant relationships.
Orexins and bipolar disorder: A review
Authors: Moya Lacasa C. , Gonzalez-Blanco L. , Martinez-Cao C. , Alvarez-Vazquez C.M. , Martin-Gil E. , García Fernández A. , Saiz P.A. , Bobes J. , Garcia-Portilla M.P.
Published: September 2022

Introduction

Bipolar disorder (BD) is a chronic deteriorating illness which has a strong impact on functionality. In the past few years, orexins have gained importance as possible biomarkers of circadian rhythms, affected in BD. Up to this date, we have not found any bibliographical review evaluating the association of orexins and BD.

Objectives

To review published literature in relation to the associaton of orexins and BD.

Methods

A bibliographical search was conducted in PubMed. Inclusion criteria were a) the study evaluated orexins in plasma or cerebrospinal fluid, and b) patients with BD were included within the subjects of study.

Reference lists of the articles that met inclusion criteria were also examined.

Results

Ten articles were retrieved from the initial search. Only three met inclusion criteria and another one was selected from the reference list examination. One study observed significantly higher levels of orexin A in plasma of BD patients versus depression and controls. Other found higher concentration of orexin A of unipolar and bipolar depression versus controls, but this result was not statistically significant. Another one did not find differences in orexin A concentration between mania, depression and controls. The remaining study detected significantly lower concentration of orexin A in BD versus depression, schizophrenia and controls.

Conclusions

Despite being heterogenous, the results point out there are differences in orexin levels in BD when compared to other diagnostic groups or controls. This sets a starting point to focus research on this subject and continue analyzing the role of orexins as biomarkers in BD.

Disclosure

No significant relationships.
The Role of Base Excision Repair in Major Depressive Disorder and Bipolar Disorder
Authors: Kucuker M. , Ozerdem A. , Ceylan D. , Cabello-Arreola A. , Ho M.C. , Joseph B. , Webb L. , Croarkin P. , Frye M. , Veldic M.
Published: September 2022

Introduction

In vivo and in vitro studies suggest that inflammation and oxidative damage may contribute to the pathogenesis of major depressive disorder (MDD) and bipolar disorder (BD). Imbalance between DNA damage and repair is an emerging research area examining pathophysiological mechanisms of these major mood disorders.

Objectives

This systematic review sought to examine current evidence on the association between mood disorders and deficits in base excision repair (BER), the primary repair mechanism for repair of oxidation-induced DNA lesions.

Methods

We conducted a comprehensive literature search of Ovid MEDLINE® Epub Ahead of Print, Ovid MEDLINE® In-Process & Other Non-Indexed Citations, Ovid MEDLINE® Daily, EMBASE (1947), and PsycINFO for studies investigating the alterations in base excision repair in patients with MDD or BD.

Results

A total of 1,364 records were identified. 1,352 records remained after duplicates were removed. 24 records were selected for full-text screening and a remaining 12 articles were included in the qualitative synthesis. SNPs (Single Nucleotide Polymorphisms) of several BER genes have been shown to be associated with MDD and BD. However, it was difficult to draw conclusions from BER gene expression studies due to conflicting findings and the small number of studies.

Conclusions

Future studies comparing DNA repair during the manic or depressive episode to remission will give us a better insight regarding the role of DNA repair in mood disorders. These alterations might be utilized as diagnostic and prognostic biomarkers as well as measuring treatment response.

Disclosure

No significant relationships.
“Delirium and COVID-19”: From Symptomatology to Laboratorial and Neuroimaging Findings”
Authors: Telles Correia D. , Novais F.
Published: September 2022

Introduction

The infection caused by the SARS-CoV-2 virus called COVID-19 may affect not only the respiratory system but also the central nervous system (CNS). Delirium is a frequent and serious condition in COVID-19 patients and may be caused by the direct invasion of the CNS or the induction of CNS inflammatory mediators or by indirect effects due to the systemic inflammatory status, other organ failure, prolonged mechanical ventilation time, immobilization but also social isolation. We aim to critically review literature reporting this syndrome in patients infected by the SARS-CoV-2 virus with a particular emphasis on reported clinical, laboratorial and neuroimaging findings. Methods: A state-of-the-art literature review was performed using PubMed, Embase and Web of Knowledge using the following keywords: delirium, COVID-19, SARS-Cov-2, neuroimaging, laboratorial findings. Results: More than 50% of patients with COVID-19 may present with delirium and in about 20% of the cases this is the primary presentation of the disorder. Previous data suggests that these patients may show a higher frequency of certain symptoms such as agitation, myoclonus, abulia, and alogia. Some distinct neuroinflammatory syndromes have been identified in patients presenting with delirium associated with the virus, namely, autoimmune encephalitis, Acute Disseminated Encephalomyelitis (ADEM) and stroke showing its potential for CNS involvement. Many of these patients present normal brain imaging, EEG and CSF findings but others have more specific laboratorial changes such as elevated creatinine kinase, elevated D-dimer levels, abnormal coagulation parameters and positive SARS-Cov-2 PCR in CSF or meningeal enhancement, ischemic stroke and perfusion changes in MRI imaging.

Disclosure

No significant relationships.
Natsukashii
Authors: Gordillo Montaño M.J. , Boned Torres S.V. , Rodriguez Rodriguez L. , De Amuedo Rincon M.
Published: September 2022

Introduction

NATSUKASHII: Japanese word that means happy nostalgia, it is the moment in which memory transports you to a beautiful memory that fills you with sweetness. NOSTALGY: (from the classical Greek [nóstos], “return”, and [algos], “pain”) feeling of sadness, suffering of thinking about something that has been had or lived in a stage and now not. In bipolar disorder, patients are more likely to complain of dysphoria than euphoria. Hypomanic periods often provide pleasant relief from depression. Patients experience this situation as pleasant, positive and longing once it has remitted, since they feel more creative, active and sociable.

Objectives

We intend to draw attention to the blurred limits of the state of euthymia, even when stable there is a sustained emotional hypersensitivity, which must be learned to identify and coexist. Behind the desire to be euthymic, in certain patients there is a desire to remain hypomanic and / or manic due to the fact that they have tasted absolute happiness.

Methods

After several interviews with stable patients, we have realized that a great majority want to re-experience the sensations of a hypomanic episode.

Results

After a bibliographic search we have realized that in the West there is no term in psychopathology that describes that longing that they verbalize as “maniac lives happier”

Conclusions

Special attention must be paid to these patients since they have less adherence to treatment and risk of abandoning it.

Disclosure

No significant relationships.
Evidence-based Pharmacological Treatment in the Maintenance Phase of the Type I Bipolar Disorder: Anticonvulsants or Antipsychotics?
Authors: Vasiliu O.
Published: September 2022

Introduction

Type I bipolar disorder (BDI) is characterized by a chronic evolution, with recurrent mood episodes that severely disrupt the overall functionality and quality of patients’ life. An adequate maintenance treatment is necessary to prevent relapses and to improve the functional prognosis of these patients.

Objectives

To find data regarding the most evidence-based therapeutic strategies in the maintenance phase of BDI.

Methods

A literature review was performed through the main electronic databases (PubMed, CINAHL, SCOPUS, EMBASE) using the search paradigm “type I bipolar disorder” AND “mood stabilizers” AND “antipsychotics” AND “anticonvulsants”. All papers published between January 2000 and August 2021 were included.

Results

The main recommendation is to continue in the maintenance phase the same medication that has proven its efficacy and tolerability in the acute phase. In BDI the most evidence-supported pharmacological approaches for the maintenance phase were lithium, valproate, lamotrigine, and carbamazepine as anticonvulsants/mood stabilizers, as well as olanzapine, quetiapine, and aripiprazole as antipsychotics. Lithium and valproate have been associated with positive influence over neuroplasticity, while antipsychotics have considerably higher metabolic adverse events. Monotherapy is recommended, but drugs associations are frequently met in clinical practice. There are no consistent data about the superiority of one class over the other, but lithium has a proven effect of decreasing the suicide rate in this population.

Conclusions

Both anticonvulsants and antipsychotics are used in the maintenance phase of the BDI, without significant differences in the efficacy rates. However, benefits and risks should be weighted for each class and each individual agent recommended.

Disclosure

No significant relationships.
Is there a relationship between clinical stage and cardiovascular disease risk in bipolar disorder?
Authors: Altınbaş K. , Kavak Sinanoğlu G.
Published: September 2022

Introduction

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in bipolar disorders(BD). The heart age of patients with BD was found to be 8.5 years higher than gender-age matched health controls. Metabolic side effects of antipsychotics, poor diet, insufficient physical activity, smoking and sedentary life style increase the risk of cardiovascular disease in bipolar patients. QRISK-3 is an approved risk classification that calculates the 10-year risk of developing a heart attack or stroke.

Objectives

This study aims to determine whether there is a difference between cardiovascular disease risk scores and clinical stages of bipolar disorder

Methods

35 outpatients that were followed up in Selcuk University Medical Faculty were evaluated. The clinical stages and qrisk3 scores were calculated.

Results

68.6% (n:24) of the patients were female. 42.9% of patients were in stage 3b (recurrent relapses, complete remission between episodes). The mean age was 36.94 ±10.46 years. The mean heart age was 50.54±17.35. The mean Q risk3 score was 5.59±8.18. There was no difference between bipolar patients at stage 2 and stage 3 in terms of age(p=0.36 and gender(p=0.73). When we compared the qrisk3 total socres and heart age of the patients in stage 2 and 3, we could not find any difference between groups (p=0.74, p=0.57 respectively).

Conclusions

Even though we could not find any difference of qrisk scores at different clinical stages of patients with BD, the CVD risk increases with the age. Prospective longitudinal follow-up studies are required to evaluate dual interaction of clinical stages and CVD risk in BD.

Disclosure

No significant relationships.
Neonatal onset of bipolar spectrum disorder through a three-generation familial study
Authors: Abdelmoula B. , Sellami S. , Keskes M. , Bouayed Abdelmoula N.
Published: September 2022

Introduction

Age at onset of pediatric bipolar spectrum disorder (BSD) is an important marker of a more severe form and a highly heritable mood/mental disorder.

Objectives

Here, we report a familial Tunisian BSD follow-up study showing a very early onset of the BSD at the neonatal period.

Methods

A 28-year-old female and her 30-year old sister were referred for genetic and psychological assessments due to recurrent depressive episodes.

Results

Psychological assessment revealed a BSD type II with episodes of hypomania for both patients. The 30-year old sister presented a mixed form of BSD coupled with autistic traits, hyposomnia and obsessive-compulsive behaviors. Intellectual and cognitive abilities were without concerns. Familial history revealed BDS among paternal relatives including the brothers’ and sisters’ father as well as all their uncles offspring’s, and their grandparents, who were consanguineous. The depressive mood was a common sign in the three generations. Personal history revealed significant signs of a very early onset of the disorder since the neonatal period for the two sisters as well as for their four paternal cousins who also presented BSD features. Familial risk of BSD in this family correlates with a variably higher personal risk of other psychiatric disorders such as anxiety, drug abuse, personality disorders, and autism spectrum disorder.

Conclusions

Environmental conditions, familial care and educational level have a strong correlation with the severity and the efficiency of cognitive management of BSD and its psychiatric comorbidities. BSD is highly heterogeneous and polygenic and personalized management has considerable clinical repercussions benefits.

Disclosure

No significant relationships.
Results of a Randomized, Double-Blinded Trial of Micronutrients and Fish Oil among Patients Diagnosed with Bipolar Disorder
Authors: Mehl-Madrona L.
Published: September 2022

Introduction

In a previous open-label study, we found that patients with bipolar disorder improved in symptom level when taking micronutrients and fish oil. We planned a randomized, double-blind, controlled trial to explore the feasibility and parameters needed for a larger clinical trial.

Objectives

We aimed to determine the parameters necessary to conduct a large-scale clinical trial through completing a feasibility study.

Methods

Patients were screened for having the diagnosis of bipolar disorder and being willing to take up to 16 micronutrient capsules and 3 fish oil capsules per day. Patients were randomized in a 3:2 ratio to micronutrients or placebo. Patients were seen monthly with assessment of the Clinical Global Impression Scale, the UKU Side Effects Scale, and a review of their medication doses. On a quarterly basis, patients completed the BASIS-24, the MYMOP-2, the Young Mania Scale, and the MADRS questionnaire

Results

The setting was a primary care clinic in Maine in the United States. The patient population was low-income and primarily rural. Disease severity was mild to moderate as only 2 patients were hospitalized during the study. All were symptomatic. One hundred twenty-five patients were screened and accepted randomization. The attrition rate was high and only 52 subjects completed 6 months of treatment. No differences were found between the two groups. We calculated that a minimum of 250 subjects would be needed to have 80% power to detect a difference. All patients improved dramatically in all measures.

Conclusions

Bipolar patients in primary care remain moderately symptomatic and will improve dramatically with monthly visits.

Disclosure

No significant relationships.
A blemish on bipolar disorder: aggressive behaviour
Authors: Zanardi R. , Manfredi E. , Attanasio F. , Carminati M. , Colombo C.
Published: September 2022

Introduction

Many studies have searched for an association between violence and psychiatric diagnoses, without providing a confirmative result.

Objectives

We have sought to deepen this topic, analysing different aspects of aggressivity, focusing on a specific diagnosis and its particular phases of illness, and looking for a correlation between psychiatric co-diagnoses and outpatients’ visits adherence.

Methods

We studied 151 bipolar type I inpatients presenting complaint, past medical and family history; we collected information about lifetime hetero/self-aggressive behaviours, irritability, agitation, suicide attempts, alcohol, or substance abuse.

Results

The overall aggressivity in our sample resulted in 11.92% of cases, while the number of aggressive episodes during euthymia decreased to 2.64%, close to the population without psychiatric disorders. Personality disorders and alcohol abuse appeared to be the main risk factors for irritability [Fig. 1]; substance abuse for both irritability and hetero-aggressive behaviour [Fig. 2]. We observed that subjects who displayed better compliance to follow-up visits exhibited a significant lower aggressive behaviour than less adherent subjects. Moreover, our data disconfirm the common conception that correlates the presence of psychotic features to violence.

Conclusions

Studying aggressive in a bipolar population, we observed that the rare episodes of aggressiveness were condensed in active phases of illness and mainly related to alcohol or substance abuse, while violent acts during long periods of wellbeing appear in line with those of the general population. We are confident our data might be helpful in deconstructing the stigma that a psychiatric diagnosis equals to violent behaviour.

Disclosure

No significant relationships.
Clinical validation of EDIT-B test for the diagnosis of bipolar disorder
Authors: Abraham J.-D. , Salvetat N. , Guerra P. , Ferrari M. , Le Guen P. , Biglia O. , Henry C. , Kessing L. , Haro J.M. , Vieta E. , Weissmann D.
Published: September 2022

Introduction

Bipolar disorder (BD) is a psychiatric disorder characterized by alternating episodes of high mood and low mood similar to depression. To differentiate BD patients from unipolar (UN) depressed patients remains a challenge and the clinical scales available failed to distinguish these 2 populations. ALCEDIAG developed EDIT-B, the first blood test able to make a differential diagnosis of BD. Based on RNA editing modifications measurement and AI, the test requires a simple blood draw and equipment available in most central laboratories. A first study on 160 UN and 95 BD patients allowed a differential diagnosis with an AUC of 0.935 and high specificity (Sp=84.6%) and sensitivity (Se=90.9%). A multicentric clinical study has been set up to validate these performances.

Objectives

The objective of this project is to run a multicentric clinical study in Europe and assess the performances of the test.

Methods

The EDIT-B project, led by Alcediag, is supported by EIT-Health grant (European institute of Innovation and Technology) and gathers 4 clinical centers in 3 countries (France, Spain, Danemark), a CRO for the clinical study management (Aixial), a CRO for the development of a diagnostic kit (Veracyte), a diagnostic lab for molecular biology analyses (Synlab), and a regulatory company (PLG).

Results

At the end of the study, the EDIT-B performance will be confirmed and the test will be CE-marked.

Conclusions

This test will address the needs of millions of patients suffering from misdiagnosis and therefore allow them to receive the correct treatment.

Disclosure

JDA, NS and DW are employees of Alcediag.