Evaluation of the correlation of serological and intradermal allergen testing with clinical history in 29 dogs with atopic dermatitis.

BACKGROUND: Limited information exists about the correlation between clinical history and positive serum (SAT) and intradermal allergen test (IDAT) results in atopic dogs. OBJECTIVES: To evaluate the correlation between clinical history and SAT/IDAT results in atopic dogs. ANIMALS: Twenty-nine client-owned dogs with nonseasonal atopic dermatitis with or without seasonal exacerbation were enrolled. MATERIALS AND METHODS: IDAT, SAT (immunoglobulin (Ig)M antibody capture enzyme-linked immunosorbent assay [MacELISA] with bromelain CCD inhibitor) and clinical information collected in a questionnaire regarding seasonal variations in pruritus affecting the dogs were performed on the same day. Two independent investigators (Inv A and Inv B) recorded IDAT results. RESULTS: The kappa coefficients agreement for positive IDAT scores between Inv A and B was substantial. The agreement between IDAT and SAT results at different ELISA absorbance units (EAU) cut-offs (>79 and ≥300) was slight and fair for both investigators, respectively. A higher agreement was observed between IDAT and SAT (≥300 EAU) than between IDAT and SAT (>79 EAU) with the exception of mite and flea allergens. There was a statistically significant association between clinical history and positive IDAT results for seasonal allergens (Inv A and Inv B, p = 0.016). There was no significance between positive SAT results and clinical history. Five (IDAT) and 12 of 13 (SAT) atopic dogs without clinical seasonal exacerbation showed positive results for seasonal allergens. CONCLUSIONS AND CLINICAL RELEVANCE: The agreement between IDAT and SAT ≥300 EAU results was fair and the agreement between IDAT and SAT >79 EAU results was slight for all allergens. Only positive IDAT results significantly correlated with clinical history.

Systematic review of caregiver burden, unmet needs and quality-of-life among informal caregivers of patients with pancreatic cancer.

PURPOSE: Informal caregivers play an important supportive care role for patients with cancer. This may be especially true for pancreatic cancer which is often diagnosed late, has a poor prognosis and is associated with a significant symptom burden. We systematically reviewed the evidence on caregiver burden, unmet needs and quality-of-life of informal caregivers to patients with pancreatic cancer. METHOD: PubMed, Medline, CINAHL and Embase databases were systematically searched on 31 August 2021. Qualitative and quantitative data on informal caregivers' experiences were extracted and coded into themes of burden, unmet needs or quality-of-life with narrative synthesis of the data undertaken. RESULTS: Nine studies (five qualitative, four quantitative), including 6023 informal caregivers, were included in the review. We categorised data into three key themes: caregiver burden, unmet needs and quality-of-life. Data on caregiver burden was organised into a single subtheme relating to symptom management as a source of burden. Data on unmet needs was organised into three subthemes need for: better clinical communication; support and briefings for caregivers; and help with navigating the health care system. Data on quality-of-life indicate large proportions of informal caregivers experience clinical levels of anxiety (33%) or depression (12%-32%). All five qualitative studies were graded as good quality; three quantitative studies were poor quality, and one was fair quality. CONCLUSION: High-quality pancreatic cancer care should consider the impacts of informal caregiving. Prospective longitudinal studies examining multiple dimensions of caregiver burden, needs, and quality-of-life would be valuable at informing supportive care cancer delivery to pancreatic cancer informal caregivers.

Adjuvant Chemotherapy in the Treatment of Intraductal Papillary Mucinous Neoplasms of the Pancreas: Systematic Review and Meta-Analysis.

BACKGROUND: The present systematic review aimed to compare survival outcomes of invasive intraductal papillary mucinous neoplasms (IIPMNs) treated with adjuvant chemotherapy versus surgery alone and to identify pathologic features that may predict survival benefit from adjuvant chemotherapy. METHOD: A systematic search of MEDLINE, PubMed, Scopus, and EMBASE was performed using the PRISMA framework. Studies comparing adjuvant chemotherapy and surgery alone for patients with IIPMNs were included. Primary endpoint was overall survival (OS). A narrative synthesis was performed to identify pathologic features that predicted survival benefits from adjuvant chemotherapy. RESULTS: Eleven studies and 3393 patients with IIPMNs were included in the meta-analysis. Adjuvant chemotherapy significantly reduced the risk of death in the overall cohort (HR 0.57, 95% CI 0.38-0.87, p = 0.009) and node-positive patients (HR 0.29, 95% CI 0.13-0.64, p = 0.002). Weighted median survival difference between adjuvant chemotherapy and surgery alone in node-positive patients was 11.6 months (95% CI 3.83-19.38, p = 0.003) favouring chemotherapy. Adjuvant chemotherapy had no impact on OS in node-negative patients (HR 0.53, 95% CI 0.20-1.43, p = 0.209). High heterogeneity (I2 > 75%) was observed in pooled estimates of hazard ratios. Improved OS following adjuvant chemotherapy was reported for patients with stage III/IV disease, tumour size > 2 cm, node-positive status, grade 3 tumour differentiation, positive margin status, tubular carcinoma subtype, and presence of perineural or lymphovascular invasion. CONCLUSION: Adjuvant chemotherapy was associated with improved OS in node-positive IIPMNs. However, the findings were limited by marked heterogeneity. Future large multicentre prospective studies are needed to confirm these findings and explore additional predictors of improved OS to guide patient selection for adjuvant chemotherapy.

Evaluation of cutaneous and circulating (serum and exosomes) levels of chemokines (CCL17, CCL22, CCL27 and CCL28) in atopic dogs and their correlation with severity of the disease.

BACKGROUND: Canine atopic dermatitis (AD) is a complex multifactorial disease characterised by an exaggerated immunological response. Little is known about the role that cutaneous and circulating chemokines play in disease severity. OBJECTIVE: To evaluate the messenger (m)RNA and protein levels of selected chemokines in skin and serum of healthy and atopic dogs, and in the atopic group to determine whether there is a correlation with disease severity. MATERIALS AND METHODS: Skin biopsies and blood samples were taken from 12 privately owned atopic [lesional (AD-L) and nonlesional (AD-NL) skin] and 12 privately owned healthy dogs. Circulating exosomes were extracted from the serum. Cutaneous and exosomal mRNA levels of CCL17, CCL22, CCL27 and CCL28 were quantified using quantitative real-time PCR. Protein levels were evaluated using canine-specific ELISA kits. The severity and extent of the clinical signs also were assessed in the atopic dogs using Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) and a validated pruritus Visual Analog Scale (pVAS). RESULTS: The expression of CCL28 exosomes in skin was greater in AD-L when compared to healthy (P = 0.019) and AD-NL (P = 0.002) samples. However, serum expression was lower in dogs with AD compared to healthy dogs (P = 0.03). A higher expression of CCL17 and CCL22 was seen in AD-L when compared to healthy skin (P = 0.018 and P = 0.019, respectively). There also was a positive correlation between clinical scores and CCL22 (AD-NL; r = 0.6, P = 0.05) and between the pruritus score and CCL22 (AD-L; r = 0.6, P = 0.05). Differences in CCL27 concentrations were not observed. CONCLUSIONS AND CLINICAL IMPORTANCE: This study suggests that CCL17, CCL22 and CCL28 may play a role in the cutaneous inflammatory response in atopic dogs. They may be considered as markers of disease severity, although further studies are needed to validate these findings.

Endoscopic transmural drainage is associated with improved outcomes in disconnected pancreatic duct syndrome: a systematic review and meta-analysis.

BACKGROUND: Disconnected pancreatic duct syndrome (DPDS) is a complication of acute necrotizing pancreatitis in the neck and body of the pancreas often manifesting as persistent pancreatic fluid collection (PFC) or external pancreatic fistula (EPF). This systematic review and pairwise meta-analysis aimed to review the definitions, clinical presentation, intervention, and outcomes for DPDS. METHODS: The PubMed, EMBASE, MEDLINE, and SCOPUS databases were systematically searched until February 2020 using the PRISMA framework. A meta-analysis was performed to assess the success rates of endoscopic and surgical interventions for the treatment of DPDS. Success of DPDS treatment was defined as long-term resolution of symptoms without recurrence of PFC, EPF, or pancreatic ascites. RESULTS: Thirty studies were included in the quantitative analysis comprising 1355 patients. Acute pancreatitis was the most common etiology (95.3%, 936/982), followed by chronic pancreatitis (3.1%, 30/982). DPDS commonly presented with PFC (83.2%, 948/1140) and EPF (13.4%, 153/1140). There was significant heterogeneity in the definition of DPDS in the literature. Weighted success rate of endoscopic transmural drainage (90.6%, 95%-CI 81.0-95.6%) was significantly higher than transpapillary drainage (58.5%, 95%-CI 36.7-77.4). Pairwise meta-analysis showed comparable success rates between endoscopic and surgical intervention, which were 82% (weighted 95%-CI 68.6-90.5) and 87.4% (95%-CI 81.2-91.8), respectively (P = 0.389). CONCLUSIONS: Endoscopic transmural drainage was superior to transpapillary drainage for the management of DPDS. Endoscopic and surgical interventions had comparable success rates. The significant variability in the definitions and treatment strategies for DPDS warrant standardisation for further research.

Systematic review and meta-analysis of risk factors of postoperative pancreatic fistula after distal pancreatectomy in the era of 2016 International Study Group pancreatic fistula definition.

BACKGROUND: Risk factors for the development of clinically relevant POPF (CR-POPF) following distal pancreatectomy (DP) need clarification particularly following the 2016 International Study Group of Pancreatic Fistula (ISGPF) definition. METHODS: A systemic search of MEDLINE, Pubmed, Scopus, and EMBASE were conducted using the PRISMA framework. Studies were evaluated for risk factors for the development CR-POPF after DP using the 2016 ISGPF definition. Further subgroup analysis was undertaken on studies ≥10 patients in exposed and non-exposed subgroups. RESULTS: Forty-three studies with 8864 patients were included in the meta-analysis. The weighted rate of CR-POPF was 20.4% (95%-CI: 17.7-23.4%). Smoking (OR 1.29, 95%-CI: 1.08-1.53, p = 0.02) and open DP (OR 1.43, 95%-CI: 1.02-2.01, p = 0.04) were found to be significant risk factors of CR-POPF. Diabetes (OR 0.81, 95%-CI: 0.68-0.95, p = 0.02) was a significant protective factor against CR-POPF. Substantial heterogeneity was observed in the comparisons of pancreatic texture and body mass index. Seventeen risk factors achieved significance in a univariate or multivariate comparison as reported by individual studies in the narrative synthesis, however, they remain difficult to interpret as statistically significant comparisons were not uniform. CONCLUSION: This meta-analysis found smoking and open DP to be risk factors and diabetes to be protective factor of CR-POPF in the era of 2016 ISGPF definition.

Genetic diversity of circumsporozoite protein in Plasmodium knowlesi isolates from Malaysian Borneo and Peninsular Malaysia.

BACKGROUND: Understanding the genetic diversity of candidate genes for malaria vaccines such as circumsporozoite protein (csp) may enhance the development of vaccines for treating Plasmodium knowlesi. Hence, the aim of this study is to investigate the genetic diversity of non-repeat regions of csp in P. knowlesi from Malaysian Borneo and Peninsular Malaysia. METHODS: A total of 46 csp genes were subjected to polymerase chain reaction amplification. The genes were obtained from P. knowlesi isolates collected from different divisions of Sabah, Malaysian Borneo, and Peninsular Malaysia. The targeted gene fragments were cloned into a commercial vector and sequenced, and a phylogenetic tree was constructed while incorporating 168 csp sequences retrieved from the GenBank database. The genetic diversity and natural evolution of the csp sequences were analysed using MEGA6 and DnaSP ver. 5.10.01. A genealogical network of the csp haplotypes was generated using NETWORK ver. 4.6.1.3. RESULTS: The phylogenetic analysis revealed indistinguishable clusters of P. knowlesi isolates across different geographic regions, including Malaysian Borneo and Peninsular Malaysia. Nucleotide analysis showed that the csp non-repeat regions of zoonotic P. knowlesi isolates obtained in this study underwent purifying selection with population expansion, which was supported by extensive haplotype sharing observed between humans and macaques. Novel variations were observed in the C-terminal non-repeat region of csp. CONCLUSIONS: The csp non-repeat regions are relatively conserved and there is no distinct cluster of P. knowlesi isolates from Malaysian Borneo and Peninsular Malaysia. Distinctive variation data obtained in the C-terminal non-repeat region of csp could be beneficial for the design and development of vaccines to treat P. knowlesi.

Rhodiola Inhibits Atrial Arrhythmogenesis in a Heart Failure Model.

INTRODUCTION: Rhodiola, a popular plant in Tibet, has been proven to decrease arrhythmia. The aim of this study was to elucidate the molecular mechanism and electrophysiological properties of rhodiola in the suppression of atrial fibrillation. METHODS: This study consisted of 3 groups as follows: Group 1: normal control rabbits (n = 5); Group 2: rabbits with heart failure (HF) created by coronary ligation and who received 2 weeks of water orally as a placebo (n = 5); and Group 3: rabbits with HF who received 2 weeks of a rhodiola 270 mg/kg/day treatment orally (n = 5). The monophasic action potential, histology, and real-time polymerase chain reaction (RT-PCR) analysis of ionic channels and PI3K/AKT/eNOS were examined. RESULTS: Compared with the HF group, attenuated atrial fibrosis (35.4 ± 17.4% vs. 16.9 ± 8.4%, P = 0.05) and improved left ventricular (LV) ejection fraction (51.6 ± 3.4% vs. 68.0 ± 0.5%, P = 0.001) were observed in the rhodiola group. The rhodiola group had a shorter ERP (85.3 ± 6.8 vs. 94.3 ± 1.2, P = 0.002), APD90 (89.3 ± 1.5 vs. 112.7 ± 0.7, P < 0.001) in the left atrium (LA), and decreased AF inducibility (0.90 ± 0.04 vs. 0.42 ± 0.04, P < 0.001) compared with the HF group. The mRNA expressions of Kv1.4, Kv1.5, Kv4.3, KvLQT1, Cav1.2, and SERCA2a in the HF LA were up-regulated after rhodiola treatment. The rhodiola-treated HF LA demonstrated higher mRNA expression of PI3K-AKT compared with the HF group. CONCLUSIONS: Rhodiola reversed LA electrical remodeling, attenuated atrial fibrosis and suppressed AF in rabbits with HF. The beneficial electrophysiological effect of rhodiola may be related to upregulation of Kv1.4, Kv1.5, Kv4.3, KvLQT1, Cav1.2, SERCA2a, and activation of PI3K/AKT signaling.

When Atrial Fibrillation Co-Exists with Coronary Artery Disease in Patients with Prior Coronary Intervention - Does Ablation Benefit?

BACKGROUND: Atrial fibrillation (AF) can be associated with an increased risk of developing coronary artery disease (CAD) due to mechanisms of inflammation, endothelial dysfunction and adverse atrial remodelling. It is unclear if adverse coronary events can be further reduced after successful catheter ablation of AF. We hypothesise that AF ablation and sinus maintenance could reduce future adverse cardiac events in patients with underlying CAD. METHODS: A total of 310 patients with drug-refractory paroxysmal AF and prior history of percutaneous coronary intervention (PCI) for underlying CAD were recruited in the retrospective case control study. Of these, 155 patients underwent AF ablation (the Ablation Group), while 155 patients received medical treatment (the Medical Group). All patients were followed up for major adverse cardiac events, including acute coronary syndrome requiring hospitalisation, stroke, pulmonary embolism and mortality. RESULTS: The clinical characteristics were comparable between the two groups, except for higher antiarrhythmic drug use in the Medical Group. During a follow-up duration of 61±32 months, all-cause mortality (8.4% vs. 1.3%, p=0.004) and the overall major adverse events (47.7% vs. 12.3%, p<0.001) were significantly higher in the Medical Group than the Ablation Group. There were also more instances of stroke (10.3% vs. 3.2%, p=0.013) and acute coronary syndrome requiring hospitalisation (29% vs. 7.1%, p<0.001) in the Medical Group than the Ablation Group. Multivariate analysis confirmed that non-ablation was an independent risk factor for major adverse events (p<0.001, HR 3.4, 95% confidence interval 1.9-5.9). CONCLUSION: In PAF patients with established CAD who underwent PCI, catheter ablation could lead to fewer major adverse cardiac events compared to medical therapy.

Molecular detection of human Plasmodium species in Sabah using PlasmoNex™ multiplex PCR and hydrolysis probes real-time PCR.

BACKGROUND: Malaria is a vector borne-parasitic disease transmitted through the bite of the infective female Anopheles mosquitoes. Five Plasmodium species have been recognized by World Health Organization (WHO) as the causative agents of human malaria. Generally, microscopic examination is the gold standard for routine malaria diagnosis. However, molecular PCR assays in many cases have shown improvement on the sensitivity and specificity over microscopic or other immunochromatographic assays. METHODS: The present study attempts to screen 207 suspected malaria samples from patients seeking treatment in clinics around Sabah state, Malaysia, using two panels of multiplex PCRs, conventional PCR system (PlasmoNex™) and real-time PCR based on hydrolysis probe technology. Discordance results between two PCR assays were further confirmed by sequencing using 18S ssu rRNA species-specific primers. RESULTS: Of the 207 malaria samples, Plasmodium knowlesi (73.4% vs 72.0%) was the most prevalent species based on two PCR assays, followed by Plasmodium falciparum (15.9% vs 17.9%), and Plasmodium vivax (9.7% vs 7.7%), respectively. Neither Plasmodium malariae nor Plasmodium ovale was detected in this study. Nine discrepant species identification based on both the PCR assays were further confirmed through DNA sequencing. Species-specific real-time PCR only accurately diagnosed 198 of 207 (95.7%) malaria samples up to species level in contrast to PlasmoNex™ assay which had 100% sensitivity and specificity based on sequencing results. CONCLUSIONS: Multiplex PCR accelerate the speed in the diagnosis of malaria. The PlasmoNex™ PCR assay seems to be more accurate than real-time PCR in the speciation of all five human malaria parasites. The present study also showed a significant increase of the potential fatal P. knowlesi infection in Sabah state as revealed by molecular PCR assays.

4:2:1 conduction of an AF initiating trigger.

A 44 year old male with idiopathic dilated cardiomyopathy was undergoing persistent atrial fibrillation (AF) ablation. Following antral ablation, AF terminated into a regular narrow complex rhythm. Earliest activation was mapped to a focus in the superior vena cava (SVC) which was conducted in a 2:1 ratio to the atria which in turn was conducted with 2:1 ratio to the ventricles, resulting in an unusual 4:2:1 conduction of the SVC tachycardia. 1:1 conduction of the SVC tachycardia to the atrium preceded initiation of AF. During AF, SVC tachycardia continued unperturbed. Sinus rhythm was restored following catheter ablation of the focus.

A prospective and randomized comparison of limited versus extensive atrial substrate modification after circumferential pulmonary vein isolation in nonparoxysmal atrial fibrillation.

INTRODUCTION: The optimal substrate ablation approach in patients with persistent atrial fibrillation (Per AF) remains unclear. This was a prospective randomized study comparing the efficacy of limited (continuous complex fractionated atrial electrogram, CFAE: <60 milliseconds) versus extensive (continuous CFAE plus variable CFAE: <120 milliseconds) atrial substrate modification in Per AF patients. METHODS AND RESULTS: We enrolled 120 Per AF patients in the study, and 30 patients with AF termination after pulmonary vein isolation (PVI) were excluded. In the remaining 90 patients, 45 were treated with limited approach (Group 1) and 45 with an extensive approach (Group 2). The end point of the study was the incidence of an atrial arrhythmia recurrence postblanking period. The patients were followed up for 15 months with 3-month clinical reviews, electrograms (ECGs), Holter recordings, and echocardiographic monitoring. Procedural AF termination and the single procedural efficacy were statistically comparable between the 2 groups (48.9% vs. 63.4% in Groups 1 and 2, respectively, P = 0.289). During the follow-up, patients who received limited ablation had a lower incidence of recurrent AFL (P = 0.04), and better reverse remodeling of the left atrium (LA, P = 0.04). After 2 procedures, the freedom from any atrial arrhythmia was better in Group 2 (62.2% vs. 87.8%, P = 0.009). Those with longstanding AF and a larger baseline LA size responded better to the extensive ablation. CONCLUSIONS: In the Per AF patients who failed to achieve AF termination after PVI alone, a specific atrial substrate modification approach targeting only continuous CFAEs could be considered as an initial ablation strategy.

Long-term outcome of catheter ablation in patients with atrial fibrillation originating from nonpulmonary vein ectopy.

INTRODUCTION: Data regarding the long-term outcome of catheter ablation in patients with nonpulmonary vein (NPV) ectopy initiating atrial fibrillation (AF) are limited. We aimed to evaluate the long-term result of patients with AF who had NPV triggers and underwent catheter ablation. METHODS AND RESULTS: The study included 660 consecutive patients (age 54 ± 11 years old, 477 males) who had undergone catheter ablation for AF. Group 1 consisted of 132 patients with AF initiating from the NPV, and group 2 consisted of 528 patients with AF initiating from pulmonary vein (PV) triggers only. Patients from Group 1 were younger than those from Group 2 (51 ± 12 years old vs 54 ± 11 years old, P = 0.001) and were more likely to be females (34.4% vs 25.8%, P = 0.049). The incidences of nonparoxysmal AF (36.4% vs 16.3%, P < 0.001) and right atrial (RA) enlargement (31.3% vs 19%, P = 0.004) were higher, and the biatrial substrates were worse in Group 1 than those in Group 2 (left atrial voltage 1.5 ± 0.7 mV vs 1.9 ± 0.7 mV, P < 0.001, RA voltage 1.6 ± 0.5 mV vs 1.8 ± 0.6 mV, P = 0.014). During a follow-up period of 46 ± 23 months, there was a higher AF recurrence rate in Group 1 than in Group 2 (57.6% vs 38.8%, P < 0.001). The independent predictors of AF recurrence were NPV trigger (P < 0.001, HR 2, 95% CI 1.4-2.85), nonparoxysmal AF (P = 0.021, HR 1.55, 95% CI 1.07-2.24), larger left atrial diameter (P = 0.002, HR 1.04, 95% CI 1.02-1.07) and worse left atrial substrate (P = 0.028, HR 1.3, 95% CI 1.03-1.64). CONCLUSION: Compared to AF originating from the PV alone, AF originating from the NPV ectopy showed a worse outcome.

Dataset of the complete genome of Streptomyces cavourensis strain 2BA6PGT isolated from sediment from the bottom of the salt lake Verkhnee Beloe (Buryatia, Russia).

The Streptomyces cavourensis strain 2BA6PGT was isolated from sediment from the bottom of the salt lake Verkhnee Beloe (Buryatia, Russia). This strain's 7,651,223 bp complete genome has a high G + C content of 72.1% and consists of 7,069 coding sequences and 315 subsystems. The 16S ribosomal RNA of isolate 2BA6PGT was most closely related to Streptomyces cavourensis strain NBRC 13026T (98.91% identity), followed by Streptomyces bacillaris strain ATCC 15855T (95.36%), Streptomyces rhizosphaericola strain 1AS2cT (94.68%), and Streptomyces pluricolorescens strain JCM 4602T (86.75%). These comparisons were supported by pairwise comparisons using average nucleotide identity (ANI) and DNA-DNA hybridization analysis. This is the first complete genome reported on Streptomyces cavourensis isolated from sediment from the bottom of the salt lake Verkhnee Beloe. The complete genome sequence has been deposited at the NCBI GenBank with an accession number CP101140.

Timeline of SARS-CoV-2 Transmission in Sabah, Malaysia: Tracking the Molecular Evolution.

BACKGROUND: The COVID-19 pandemic poses an unprecedented public health challenge in Malaysia. The impact of COVID-19 varies between countries, including geographically divided states within a country. The deadly transmission of COVID-19 has taken a heavy toll in Sabah, Malaysia's third most populous state, contributing nearly 10% to the recorded national death toll as of 31 December 2022. Although several SARS-CoV-2 genome sequences have been analysed in Malaysia, molecular epidemiology data from Sabah focusing on the diversity and evolution of SARS-CoV-2 variants are still lacking. This study examines the major SARS-CoV-2 variants and emerging mutations from Sabah, the Malaysian Borneo, which is geographically divided from West Malaysia by the South China Sea. METHODS: A total of 583 COVID-19 samples were subjected to whole genome sequencing and analysed with an additional 1123 Sabah COVID-19 sequences retrieved from the GISAID EpiCoV consortium. Nextclade and Pangolin were used to classify these sequences according to the clades and lineages. To determine the molecular evolutionary characteristics, Bayesian time-scaled phylogenetic analysis employing the maximum likelihood algorithm was performed on selected SARS-CoV-2 genome sequences, using the Wuhan-Hu-1 sequence as a reference. RESULTS: Sabah was affected starting from the second COVID-19 wave in Malaysia, and the early sequences were classified under the O clade. The clade was gradually replaced during subsequent waves by G, GH, GK and GRA, with the latter being dominant as of December 2022. Phylogenetically, the Delta isolates in this study belong to the three main subclades 21A, 21J and 21I, while Omicron isolates belong to 21M, 21L and 22B. The time-scaled phylogeny suggested that SARS-CoV-2 introduced into Sabah originated from Peninsular Malaysia in early March 2020, and phylodynamic analysis indicated that increased viral spread was observed in early March and declined in late April, followed by an evolutionary stationary phase in June 2020. CONCLUSION: Continuous molecular epidemiology of SARS-CoV-2 in Sabah will provide a deeper understanding of the emergence and dominance of each variant in the locality, thus facilitating public health intervention measures.

A Retrospective Evaluation of the Steroid-Sparing Effect of Oral Modified Ciclosporin for Treatment of Canine Pemphigus Foliaceus.

The efficacy of ciclosporin as an adjuvant immunosuppressant administered with glucocorticoids (GCs) for induction of canine PF remission is unknown. This study is a retrospective review of medical records from 2015 to 2020 to evaluate the therapeutic outcomes of 11 PF dogs treated with oral modified ciclosporin and GCs. Concurrent GCs were given with ciclosporin to all PF dogs. Nine dogs (9/11) achieved complete remission (CR); five dogs received ciclosporin at a mean dose of 6.2 mg/kg/day; and four dogs received a combination of ciclosporin and ketoconazole at a mean dose of 3 mg/kg/day, respectively. Two dogs (2/11) showed only 25% or poor response, with the development of new PF lesions during treatment. The mean duration of ciclosporin therapy for nine dogs to achieve CR was 65 days (median 57 days, range 24-119 days). Slow tapering of oral GCs while continuing ciclosporin at the same dose and frequency in nine dogs with CR led to recurrence of PF lesions in four dogs, whereas, in five dogs, oral glucocorticoids were discontinued without a PF flare. Oral modified ciclosporin combined with GCs achieved CR in 9 out of 11 PF dogs during the induction phase in this study.

An Updated Review on the Role of Single Nucleotide Polymorphisms in COVID-19 Disease Severity: A Global Aspect.

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and recently has become a serious global pandemic. Age, gender, and comorbidities are known to be common risk factors for severe COVID-19 but are not enough to fully explain the magnitude of their effect on the risk of severity of the disease. Single nucleotide polymorphisms (SNPs) in several genes have been reported as a genetic factor contributing to COVID-19 severity. This comprehensive review focuses on the association between SNPs in four important genes and COVID-19 severity in a global aspect. We discuss a total of 39 SNPs in this review: five SNPs in the ABO gene, nine SNPs in the angiotensin-converting enzyme 2 (ACE2) gene, 19 SNPs in the transmembrane protease serine 2 (TMPRSS2) gene, and six SNPs in the toll-like receptor 7 (TLR7) gene. These SNPs data could assist in monitoring an individual's risk of severe COVID-19 disease, and therefore personalized management and pharmaceutical treatment could be planned in COVID-19 patients.

The Effects of NLRP3 Inflammasome Inhibition in Experimental Acute Pancreatitis: A Systematic Review and Meta-Analysis.

ABSTRACT: Acute pancreatitis (AP) is an inflammatory disease, and NLRP3 inflammasome activation is involved in the pathogenesis of AP. Previous research showed that inhibition of NLRP3 inflammasome may exert protective effects on animal models of AP and reduces disease severity. The aim of this systematic review and meta-analysis is to evaluate the effects of drug treatment of NLRP3 inflammasome on the outcomes of experimental AP. PubMed, Embase, Medline, and Web of Science databases were searched for relevant articles without language restrictions. The main outcomes for this study included local pancreatic injury, the incidence of systemic inflammatory responses, and the incidence of organ failure. Twenty-eight animal studies including 556 animals with AP were included in the meta-analysis. Compared with controls, inhibition of NLRP3 inflammasome significantly reduced the pancreatic histopathological scores, serum amylase, and lipase levels. In addition, inhibition of NLRP3 inflammasome reduced the levels of circulating inflammatory cytokines, as well as mitigating severity of AP-associated acute lung injury and acute intestinal injury. To conclude, inhibition of NLRP3 inflammasome has protective effects on AP by mitigating organ injury and systemic inflammation in animal studies, indicating that NLRP3 inflammasome holds promise as a target for specific AP therapy.

Hong Kong's new wave of migration: socio-political factors of individuals' intention to emigrate.

With a recent surge in the outward movement of the population, a new wave of emigration has been suggested to have started in Hong Kong. It is speculated that recent socio-political changes in Hong Kong may have contributed to this phenomenon. Therefore, five socio-political variables-mobility, sense of place, trust and confidence in the law and the legal system, global citizenship, and perception of inequality-are employed in this study as proposed determinants to investigate the intention of Hong Kong residents to migrate to mainland China and to other international destinations. A random telephone questionnaire survey representative of the local population was conducted, with a total of 801 valid samples collected. Stepwise multiple regression analysis was carried out. The results showed that all five proposed socio-political variables successfully predicted people's migration intention to mainland China and to foreign countries, with important variations between the two choices. Our results carry strong implications for understanding people's concerns behind their intention to emigrate. Further, our findings present a challenge for Hong Kong; society may gradually be failing to accommodate individuals with diverse perceptions and values, particularly in terms of trust and confidence in the law and the legal system, and individuals' sense of global citizenship.

Risk Association, Linkage Disequilibrium, and Haplotype Analyses of ß-Like Globin Gene Polymorphisms with Malaria Risk in the Sabah Population of Malaysian Borneo.

Single nucleotide polymorphisms (SNPs) in the ß-like globin gene of the human hosts to the risk of malaria are unclear. Therefore, this study investigates these associations in the Sabah population, with a high incidence of malaria cases. In brief, DNA was extracted from 188 post-diagnostic blood samples infected with Plasmodium parasites and 170 healthy controls without a history of malaria. Genotyping of the ß-like globin C-158T, G79A, C16G, and C-551T SNPs was performed using a polymerase chain reaction-restriction fragment length polymorphism approach. Risk association, linkage disequilibrium (LD), and haplotype analyses of these SNPs were assessed. This study found that the variant allele in the C-158T and C16G SNPs were protective against malaria infections by 0.5-fold, while the variant allele in the G79A SNP had a 6-fold increased risk of malaria infection. No SNP combination was in perfect LD, but several haplotypes (CGCC, CGCT, and CGGC) were identified to link with different correlation levels of malaria risk in the population. In conclusion, the C-158T, G79A, and C16G SNPs in the ß-like globin gene are associated with the risk of malaria. The haplotypes (CGCC, CGCT, and CGGC) identified in this study could serve as biomarkers to estimate malaria risk in the population. This study provides essential data for the design of malaria control and management strategies.