Predicting gallstone pancreatitis in HIV infected patients.

BACKGROUND: Human immunodeficiency virus (HIV) infection, low cluster of differentiation (CD)4 counts and antiretroviral therapy can cause cholestasis and raised transaminases. In acute pancreatitis, this may render biochemical predictors of a gallstone aetiology inaccurate. METHODS: In a prospective observational study, acute pancreatitis was diagnosed by standard criteria. Cholecystolithiasis and bile duct diameter were diagnosed by ultrasound. Cholestasis was defined as two of the following: bilirubin ≥ 21 umol/l, γ glutamyl transferase ≥ 78 U/l, alkaline phosphatase ≥ 121 U/l. Cholangitis was defined as cholestasis and any two sepsis criteria: (temperature > 38˚C, WCC > 12.6 ×109/L, pulse > 90 beats/min). Cholangitis, cholestasis, and bile duct diameter greater that 1 cm were indications for endoscopic retrograde cholangiopancreatography (ERCP). These parameters' ability to predict gallstone pancreatitis (GSP) and choledocholithiasis were compared in HIV+ve and HIV-ve patients. RESULTS: Sixty-two (26%) of 216 patients had GSP. Twenty four were HIV+ve patients. More HIV+ve patients had cholestasis (p = 0.059) and ERCP (p = 0.004). In HIV+ve patients alanine aminotransferase (ALT) > 100 U/L, gamma glutamyl transferase (GGT) > 2 upper limit of normal and cholestasis had a negative predictive value of 92%, 96.7% and 95.2% respectively. In HIV-ve patients, negative predictive value (NPV) was 84%, 83.8% and 84.6% respectively. Bile duct stones were demonstrated at ERCP in 6 (25%) and 3 (8%) of HIV+ve and HIV-ve patients respectively (p = 0.077). Five of 14 ERCP patients had no bile duct stones. HIV+ve and HIV-ve groups had two deaths each. CONCLUSION: Absence at presentation of the abnormal parameters analysed were good predictors of a non-gallstone aetiology particularly in HIV+ve patients. Prior, magnetic resonance cholangiopancreatography (MRCP) or endoscopic ultrasound (EUS) would reduce the number of non-therapeutic ERCPs.

Dynamic correction of dual-energy x-ray absorptiometry images improves chain speed prediction of lamb composition in abattoirs.

A prototype, on-line Dual Energy X-ray Absorptiometer (DXA) has shown high precision of the prediction of carcass composition for the purpose of improved sheep meat grading in the Australian lamb supply chain, albeit with small inaccuracies over time. These inaccuracies were present across hours, and more significantly across days, which were unacceptable for any accreditation of this device as an objective carcass measurement tool in Australia. This inaccuracy demanded the creation of a novel image-processing algorithm for the prototype DXA. This DXA was tested for repeatability of predictions of lamb carcass composition over minutes, hours, and days, using two developed image processing algorithms. There was high immediate repeatability for both algorithms when predicting lean muscle % in 40 lamb carcasses, with a maximum CV of 0.65% over five repeated scans. There was a decrease in the CV of the prediction of lean muscle % of 30 lambs scanned three times over a 48-h period from 5.93 to 1.19% when the superior algorithm was used. The inaccuracies of lean muscle % predictions were associated with increases in the unattenuated space pixel values in DXA images. Improvements of the current algorithm are required to demonstrate repeatability over time for the purpose of accreditation within the Australian sheep meat industry, and for possible expansion of this technology into international supply chains.

Mechanical Properties and Failure Mode of Proximal Screw Fixation Technique Using Locking Compression Plate for Proximal Interphalangeal Arthrodesis in Horses: An Ex Vivo Study.

OBJECTIVE: The aim of this study was to measure the mechanical properties and failure mode of an ex vivo model of proximal interphalangeal arthrodesis in horses with different methods of proximal screw fixation using a locking compression plate. STUDY DESIGN: Pastern joint arthrodesis with a 3-hole 4.5-mm narrow locking compression plate was performed on 20 forelimbs of equine cadavers, randomized into four groups based on the fixation method and type of proximal screw used: unicortical cortex, bicortical cortex, unicortical locking, bicortical locking. Single-cycle axial compression testing was conducted until failure. The frequency of implant plastic deformation was recorded. Bone failure analysis was performed through computed tomography examinations and fractal analysis. RESULTS: There were no differences in the analysed mechanical variables and fractal dimension among the groups. Transarticular screws showed a higher frequency of deformation (75%) regardless of the group. Both unicortical locking and bicortical locking groups deformed the plate more frequently. CONCLUSION: The type of screw used in the proximal hole of the locking compression plate and its method of anchoring in the proximal phalanx do not affect the mechanical properties of pastern arthrodesis in equine cadavers subjected to single-cycle axial compression tests until failure.

A new lineage nomenclature to aid genomic surveillance of dengue virus.

Dengue virus (DENV) is currently causing epidemics of unprecedented scope in endemic settings and expanding to new geographical areas. It is therefore critical to track this virus using genomic surveillance. However, the complex patterns of viral genomic diversity make it challenging to use the existing genotype classification system. Here we propose adding two sub-genotypic levels of virus classification, named major and minor lineages. These lineages have high thresholds for phylogenetic distance and clade size, rendering them stable between phylogenetic studies. We present an assignment tool to show that the proposed lineages are useful for regional, national and sub-national discussions of relevant DENV diversity. Moreover, the proposed lineages are robust to classification using partial genome sequences. We provide a standardized neutral descriptor of DENV diversity with which we can identify and track lineages of potential epidemiological and/or clinical importance. Information about our lineage system, including methods to assign lineages to sequence data and propose new lineages, can be found at: dengue-lineages.org.

BMP6 and VDR gene polymorphisms are associated with osteonecrosis in a sickle cell anaemia cohort.

The occurrence and severity of osteonecrosis in sickle cell anaemia (SCA) vary due to risk factors, including genetic modifiers. Bone morphogenetic proteins (BMPs), particularly BMP6, and the vitamin D receptor (VDR) play key roles in cartilage and bone metabolism, making them potential contributors to orthopaedic outcomes in SCA. Here, we evaluated the association of polymorphisms in BMP6 (rs3812163, rs270393 and rs449853) and VDR (FokI rs2228570 and Cdx2 rs11568820) genes with osteonecrosis risk in a Brazilian SCA cohort. A total of 177 unrelated SCA patients were selected. The AA genotype of BMP6 rs3812163 was independently associated with a lower osteonecrosis risk (p = 0.015; odds ratio (OR): 0.38; 95% confidence interval (CI): 0.18-0.83) and with the long-term cumulative incidence of osteonecrosis (p = 0.029; hazard ratio: 0.56, 95% CI: 0.34-0.94). The VDR rs2228570 TT genotype was independently associated with a lower osteonecrosis risk (p = 0.039; OR: 0.14; 95% CI: 0.02-0.90). In summary, our results provide evidence that BMP6 rs3812163 and the VDR rs2228570 might be implicated in osteonecrosis pathophysiology in SCA and might help identify individuals at high risk.

Ultimobranchial body cyst in an adult horse: clinical, histopathologic, and immunohistochemical features.

A 9-y-old Mangalarga Marchador gelding was referred to a veterinary hospital because of a swelling on the upper right side of the neck. Ultrasound examination revealed a multilocular structure adjacent to the thyroid gland with low echogenic content suggestive of fluid. The mass was removed surgically. Histologically, the cystic cavities in the surgical sample were filled with abundant eosinophilic secreta and lined by cuboidal, segmentally ciliated, columnar epithelium with interspersed goblet cells. Segmental crowding of the multilayered lining of the cyst was noted. Immunohistochemistry suggested the presence of both C cells and follicular cells, given the positivity of the immunomarkers calcitonin and TTF-1, respectively. The histogenesis of ultimobranchial cysts is uncertain. Based on clinical, histopathologic, and immunohistochemical identification, the cystic structure in this case is compatible with an ultimobranchial body cyst.

Biomass and carbon balance in a dry tropical forest area in northeast Brazil.

Forest ecosystems play an important role in mitigating the concentration increase of carbon dioxide (CO2) in the atmosphere through carbon sequestration by plants and its storage in biomass and soil. The objective was to determine the aerial biomass carbon stock in a dry tropical forest in Brazil. It was developed between 2012 to 2015, in an area with an advanced regeneration stage (50 years) in the semi-arid region of Pernambuco and it was used 40 permanent plots (400 m²) distant 80 m apart, with 50 m from the border, totaling 1.6 ha of the area to sample the shrubby-arboreal component, where all individuals with circumference at breast height (1.30 m of the soil) equal or greater than 6 cm were identified, measured and labeled in 2012 and remeasured in 2015. It was calculated the biomass and carbon stocks through developed equations available in the literature. The results showed that the total biomass and carbon stock in the first year was 27.97 e 12.92 Mg.ha-1 while in 2015 it was 18.49 and 8.39 Mg.ha-1 respectively. The results showed a biomass and carbon stock reduction of more than 30% in the period evaluated, even this, the area manages to present values within the expected pattern for the region, assuring the importance of sustainable forest management of these native/natural vegetation areas.

Thinking out of the box: revisiting health surveillance based on medical records.

Despite the considerable advances in the last years, the health information systems for health surveillance still need to overcome some critical issues so that epidemic detection can be performed in real time. For instance, despite the efforts of the Brazilian Ministry of Health (MoH) to make COVID-19 data available during the pandemic, delays due to data entry and data availability posed an additional threat to disease monitoring. Here, we propose a complementary approach by using electronic medical records (EMRs) data collected in real time to generate a system to enable insights from the local health surveillance system personnel. As a proof of concept, we assessed data from São Caetano do Sul City (SCS), São Paulo, Brazil. We used the "fever" term as a sentinel event. Regular expression techniques were applied to detect febrile diseases. Other specific terms such as "malaria," "dengue," "Zika," or any infectious disease were included in the dictionary and mapped to "fever." Additionally, after "tokenizing," we assessed the frequencies of most mentioned terms when fever was also mentioned in the patient complaint. The findings allowed us to detect the overlapping outbreaks of both COVID-19 Omicron BA.1 subvariant and Influenza A virus, which were confirmed by our team by analyzing data from private laboratories and another COVID-19 public monitoring system. Timely information generated from EMRs will be a very important tool to the decision-making process as well as research in epidemiology. Quality and security on the data produced is of paramount importance to allow the use by health surveillance systems.

HIV associated malignancies presenting as acute pancreatitis: a case series.

BACKGROUND: Acute pancreatitis (AP) may be the presenting symptom in a small percentage of patients harbouring pancreatic or extra pancreatic tumours. This case series aims to describe the pathological spectrum of tumours detected in two AP cohorts from a high HIV-endemic region. METHODS: Prospectively collected databases of patients admitted with AP over two periods 2001 to 2010 and 2013 to 2015, were retrospectively evaluated to detect those with pancreatic and extra-pancreatic tumours. The diagnosis of AP was by standard criteria. HIV infection and CD4 counts were routinely tested for in the latter period and only tested on clinical grounds in the initial period. CT scan was performed when there was diagnostic doubt, predicted severe disease, and failure to improve clinically after one week. Demographic, clinical, investigative, and pathology details were collected and presented. RESULTS: HIV-positive patients admitted with AP were 106 (17%) of 628 in the first period and 90 (38%) of 238 of the second period. No tumours were diagnosed in the HIV-negative patients. Seven of the HIV-positive patients had tumours diagnosed at endoscopy, CT scan, and endoscopic retrograde cholangiography. Of the seven HIV-positive patients with tumours, two patients had a CD4 count above 200. There were four patients with lymphoma involving the pancreatic head, three having associated cholestasis, and three patients with Kaposi's Sarcoma. One Kaposi's sarcoma patient died three months after presentation. One patient with lymphoma died on day 14 and another two months after initial presentation, and the remaining four patients were referred to oncology. CONCLUSION: Despite their rarity (< 4%), when HIV-positive patients with low CD4 count and cholestasis present with AP, tumours should be suspected and evaluated by cross sectional imaging and endoscopic ultrasound.

Previous fracture and subsequent fracture risk: a meta-analysis to update FRAX.

A large international meta-analysis using primary data from 64 cohorts has quantified the increased risk of fracture associated with a previous history of fracture for future use in FRAX. INTRODUCTION: The aim of this study was to quantify the fracture risk associated with a prior fracture on an international basis and to explore the relationship of this risk with age, sex, time since baseline and bone mineral density (BMD). METHODS: We studied 665,971 men and 1,438,535 women from 64 cohorts in 32 countries followed for a total of 19.5 million person-years. The effect of a prior history of fracture on the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture, and hip fracture alone was examined using an extended Poisson model in each cohort. Covariates examined were age, sex, BMD, and duration of follow-up. The results of the different studies were merged by using the weighted ß-coefficients. RESULTS: A previous fracture history, compared with individuals without a prior fracture, was associated with a significantly increased risk of any clinical fracture (hazard ratio, HR = 1.88; 95% CI = 1.72-2.07). The risk ratio was similar for the outcome of osteoporotic fracture (HR = 1.87; 95% CI = 1.69-2.07), major osteoporotic fracture (HR = 1.83; 95% CI = 1.63-2.06), or for hip fracture (HR = 1.82; 95% CI = 1.62-2.06). There was no significant difference in risk ratio between men and women. Subsequent fracture risk was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any clinical fracture (14%), osteoporotic fracture (17%), and for hip fracture (33%). The risk ratio for all fracture outcomes related to prior fracture decreased significantly with adjustment for age and time since baseline examination. CONCLUSION: A previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by BMD. The effect is similar in men and women. Its quantitation on an international basis permits the more accurate use of this risk factor in case finding strategies.

Risk factors for long coronavirus disease 2019 (long COVID) among healthcare personnel, Brazil, 2020-2022.

OBJECTIVE: To determine risk factors for the development of long coronavirus disease 2019 (COVID-19) in healthcare personnel (HCP). METHODS: We conducted a case-control study among HCP who had confirmed symptomatic COVID-19 working in a Brazilian healthcare system between March 1, 2020, and July 15, 2022. Cases were defined as those having long COVID according to the Centers for Disease Control and Prevention definition. Controls were defined as HCP who had documented COVID-19 but did not develop long COVID. Multiple logistic regression was used to assess the association between exposure variables and long COVID during 180 days of follow-up. RESULTS: Of 7,051 HCP diagnosed with COVID-19, 1,933 (27.4%) who developed long COVID were compared to 5,118 (72.6%) who did not. The majority of those with long COVID (51.8%) had 3 or more symptoms. Factors associated with the development of long COVID were female sex (OR, 1.21; 95% CI, 1.05-1.39), age (OR, 1.01; 95% CI, 1.00-1.02), and 2 or more SARS-CoV-2 infections (OR, 1.27; 95% CI, 1.07-1.50). Those infected with the SARS-CoV-2 δ (delta) variant (OR, 0.30; 95% CI, 0.17-0.50) or the SARS-CoV-2 o (omicron) variant (OR, 0.49; 95% CI, 0.30-0.78), and those receiving 4 COVID-19 vaccine doses prior to infection (OR, 0.05; 95% CI, 0.01-0.19) were significantly less likely to develop long COVID. CONCLUSIONS: Long COVID can be prevalent among HCP. Acquiring >1 SARS-CoV-2 infection was a major risk factor for long COVID, while maintenance of immunity via vaccination was highly protective.

The utility of the bedside index of severity in acute pancreatitis at prognosticating adverse outcomes.

BACKGROUND: Identification of at-risk patients with acute pancreatitis (AP) early on in the course of hospital admission remains a challenge. Early identification of these patients can facilitate early referral to tertiary hospitals with skilled multidisciplinary teams (MDTs) and high-dependency health care facilities. This study retrospectively reviewed the ability of the bedside index of severity in acute pancreatitis (BISAP) score and other biochemical markers to predict organ failure and mortality in acute pancreatitis. METHODS: All patients presenting to Grey's Hospital with AP between 2012 and 2020 were included in the study. The BISAP score and other biomarkers were evaluated at presentation in predicting organ failure (≥ 48 hours duration) and mortality. RESULTS: A total of 235 patients were included in the study. A total of 144 (61%) were male and 91 (39%) were female. Alcohol (81%) and gallstones (69%) were the commonest aetiological factors amongst males and females respectively. A total of 42 (29%) males and 10 (11%) females developed organ failure during their hospital stay. The mortality rate was 11.8% for males, 6.59% for females, with an overall mortality of 9.8%. A BISAP score of 2 had a sensitivity of 87.98% and specificity of 59.62% at predicting organ failure (positive predictive value [PPV] = 88.46%, negative predictive value [NPV] = 58.49%, 95% confidence interval [CI], p = 0.001). A BISAP score of 3 and above had a sensitivity of 98.11% and specificity of 69.57% at predicting mortality (PPV = 96.74%, NPV = 80%, 95% CI, p = 0.001). A multivariate analysis of biomarkers bicarbonate, base excess, lactate, urea and creatinine either failed to reach statistical significance or had specificity that is too low to prognosticate organ failure and mortality. CONCLUSION: The BISAP score has limitations at predicting organ failure, but it is a reliable tool for predicting mortality in AP. Due to its simplicity of use, it should be used in resource-constrained settings to triage at-risk patients in smaller hospitals, for early referral to tertiary hospitals.

Phylogeographic reconstruction of the emergence and spread of Powassan virus in the northeastern United States.

Powassan virus is an emerging tick-borne virus of concern for public health, but very little is known about its transmission patterns and ecology. Here, we expanded the genomic dataset by sequencing 279 Powassan viruses isolated from Ixodes scapularis ticks from the northeastern United States. Our phylogeographic reconstructions revealed that Powassan virus lineage II was likely introduced or emerged from a relict population in the Northeast between 1940 and 1975. Sequences strongly clustered by sampling location, suggesting a highly focal geographical distribution. Our analyses further indicated that Powassan virus lineage II emerged in the northeastern United States mostly following a south-to-north pattern, with a weighted lineage dispersal velocity of ~3 km/y. Since the emergence in the Northeast, we found an overall increase in the effective population size of Powassan virus lineage II, but with growth stagnating during recent years. The cascading effect of population expansion of white-tailed deer and I. scapularis populations likely facilitated the emergence of Powassan virus in the northeastern United States.

Nasal host response-based screening for undiagnosed respiratory viruses: a pathogen surveillance and detection study.

BACKGROUND: Symptomatic patients who test negative for common viruses are an important possible source of unrecognised or emerging pathogens, but metagenomic sequencing of all samples is inefficient because of the low likelihood of finding a pathogen in any given sample. We aimed to determine whether nasopharyngeal CXCL10 screening could be used as a strategy to enrich for samples containing undiagnosed viruses. METHODS: In this pathogen surveillance and detection study, we measured CXCL10 concentrations from nasopharyngeal swabs from patients in the Yale New Haven health-care system, which had been tested at the Yale New Haven Hospital Clinical Virology Laboratory (New Haven, CT, USA). Patients who tested negative for a panel of respiratory viruses using multiplex PCR during Jan 23-29, 2017, or March 3-14, 2020, were included. We performed host and pathogen RNA sequencing (RNA-Seq) and analysis for viral reads on samples with CXCL10 higher than 1 ng/mL or CXCL10 testing and quantitative RT-PCR (RT-qPCR) for SARS-CoV-2. We used RNA-Seq and cytokine profiling to compare the host response to infection in samples that were virus positive (rhinovirus, seasonal coronavirus CoV-NL63, or SARS-CoV-2) and virus negative (controls). FINDINGS: During Jan 23-29, 2017, 359 samples were tested for ten viruses on the multiplex PCR respiratory virus panel (RVP). 251 (70%) were RVP negative. 60 (24%) of 251 samples had CXCL10 higher than 150 pg/mL and were identified for further analysis. 28 (47%) of 60 CXCL10-high samples were positive for seasonal coronaviruses. 223 (89%) of 251 samples were PCR negative for 15 viruses and, of these, CXCL10-based screening identified 32 (13%) samples for further analysis. Of these 32 samples, eight (25%) with CXCL10 concentrations higher than 1 ng/mL and sufficient RNA were selected for RNA-Seq. Microbial RNA analysis showed the presence of influenza C virus in one sample and revealed RNA reads from bacterial pathobionts in four (50%) of eight samples. Between March 3 and March 14, 2020, 375 (59%) of 641 samples tested negative for 15 viruses on the RVP. 32 (9%) of 375 samples had CXCL10 concentrations ranging from 100 pg/mL to 1000 pg/mL and four of those were positive for SARS-CoV-2. CXCL10 elevation was statistically significant, and a distinguishing feature was found in 28 (8%) of 375 SARS-CoV-2-negative samples versus all four SARS-CoV-2-positive samples (p=4·4 × 10-5). Transcriptomic signatures showed an interferon response in virus-positive samples and an additional neutrophil-high hyperinflammatory signature in samples with high amounts of bacterial pathobionts. The CXCL10 cutoff for detecting a virus was 166·5 pg/mL for optimal sensitivity and 1091·0 pg/mL for specificity using a clinic-ready automated microfluidics-based immunoassay. INTERPRETATION: These results confirm CXCL10 as a robust nasopharyngeal biomarker of viral respiratory infection and support host response-based screening followed by metagenomic sequencing of CXCL10-high samples as a practical approach to incorporate clinical samples into pathogen discovery and surveillance efforts. FUNDING: National Institutes of Health, the Hartwell Foundation, the Gruber Foundation, Fast Grants for COVID-19 research from the Mercatus Center, and the Huffman Family Donor Advised Fund.

Supramolecular structure organization and rheological properties modulate the performance of hyaluronic acid-loaded thermosensitive hydrogels as drug-delivery systems.

The challenges for developing new pharmaceutical formulations based on natural and synthetic polymers has led to innovation into the design of systems responsive environmental stimuli such as temperature. However, the presence of hydrophilic or hydrophobic molecules, charged groups, or metallic elements can affect their structural behavior and their biopharmaceutical performance This work aims to study and characterize the morphology and structure of polymeric formulations based on Poloxamer (PL) 407 (15 % and 30 % m/v) and its binary with PL 338 (15 % PL 407 + 15 % PL 338) and hyaluronic acid (0.5 % m/v), as drug delivery systems of local anesthetic bupivacaine (0.5 % m/v) and ropivacaine (0.5 % m/v) hydrochloride. For this, it was performed SANS analysis for determination of supramolecular organization and lattice parameters; calorimetry was done to characterize their thermodynamic parameters; rheological analysis flow curve, consistency and adhesion calculation, Maxwell model study. Also, it was performed drug release profiles and calculation of diffusion coefficients. It was identified lamellar structures in PL 407 15 % formulations, and coexistence of cubic and hexagonal phases in PL 407 30 % and binary formulations, however hyaluronic acid, bupivacaine or ropivacaine seem do not affect the type of supramolecular structure. In addition, these additives can modulate viscosity among poloxamers chains, increasing micelle-micelle interactions as it happens in presence of bupivacaine. On the other hand, addition of hyaluronic acid can promote increased structural stabilization by hydrophilic interactions between hyaluronic and micellar corona. It reflects the ability how to control the drug release, as in case of binary system that retained bupivacaine for longer time than other systems, as well it happens when hyaluronic acid is added in PL 407 15 % and PL 407 30 %.

HIV associated malignancies presenting as acute pancreatitis: a case series.

BACKGROUND: Acute pancreatitis (AP) may be the presenting symptom in a small percentage of patients harbouring pancreatic or extra pancreatic tumours. This case series aims to describe the pathological spectrum of tumours detected in two AP cohorts from a high HIV-endemic region. METHODS: Prospectively collected databases of patients admitted with AP over two periods 2001 to 2010 and 2013 to 2015, were retrospectively evaluated to detect those with pancreatic and extra-pancreatic tumours. The diagnosis of AP was by standard criteria. HIV infection and CD4 counts were routinely tested for in the latter period and only tested on clinical grounds in the initial period. CT scan was performed when there was diagnostic doubt, predicted severe disease, and failure to improve clinically after one week. Demographic, clinical, investigative, and pathology details were collected and presented. RESULTS: HIV-positive patients admitted with AP were 106 (17%) of 628 in the first period and 90 (38%) of 238 of the second period. No tumours were diagnosed in the HIV-negative patients. Seven of the HIV-positive patients had tumours diagnosed at endoscopy, CT scan, and endoscopic retrograde cholangiography. Of the seven HIV-positive patients with tumours, two patients had a CD4 count above 200. There were four patients with lymphoma involving the pancreatic head, three having associated cholestasis, and three patients with Kaposi's Sarcoma. One Kaposi's sarcoma patient died three months after presentation. One patient with lymphoma died on day 14 and another two months after initial presentation, and the remaining four patients were referred to oncology. CONCLUSION: Despite their rarity (< 4%), when HIV-positive patients with low CD4 count and cholestasis present with AP,tumours should be suspected and evaluated by cross sectional imaging and endoscopic ultrasound.

Spectrum and surgical outcomes of gastrointestinal stromal tumours.

BACKGROUND: Surgery and imatinib are the mainstays of the management of gastrointestinal stromal tumours (GIST). This study aimed to analyse the outcomes in the management of GIST utilising surgery and imatinib. METHODS: Progression-free survival (PFS) and overall survival (OS) were analysed in relation to imatinib therapy, location of tumour, resection margins, type and extent of surgery. Imatinib was administered in the neoadjuvant (maximum 12 months) and adjuvant setting (minimum 36 months) and until disease progression or drug intolerance. Disease response was assessed with the Choi criteria. Survival analysis included calculation of PFS, OS and Kaplan-Meier curves. RESULTS: Sixty-two patients were reviewed and 56 had surgical resection. The median age (range) was 58.5 (8-95) years. The median PFS and OS (IQR) was 24.0 (0-52.0) and 41.0 (15.0-74.0) months, respectively. Thirty-nine (70%) patients were treated with imatinib, with 21 of these in a neoadjuvant setting. In the patients undergoing surgery, surgical margins were R0, R1 and R2 in 41 (75%), eight (15%) and six (11%) respectively. There was an insignificant difference in the overall survival in these three groups. For those having liver metastasectomy and multivisceral resection, the PFS and OS were 32.5 (17.5-60.3) and 28.5 (5.75-49.8) (p = 0.008), and 96.0 (58.5-116) and 80 (50.5-92.3) months (p = 0.033), respectively. CONCLUSION: Whilst the numbers were small, certain trends were observed. Surgery in combination with imatinib offers survival benefit in patients undergoing R0, R1, R2, liver metastases and multivisceral resections.

Global disparities in SARS-CoV-2 genomic surveillance.

Genomic sequencing is essential to track the evolution and spread of SARS-CoV-2, optimize molecular tests, treatments, vaccines, and guide public health responses. To investigate the global SARS-CoV-2 genomic surveillance, we used sequences shared via GISAID to estimate the impact of sequencing intensity and turnaround times on variant detection in 189 countries. In the first two years of the pandemic, 78% of high-income countries sequenced >0.5% of their COVID-19 cases, while 42% of low- and middle-income countries reached that mark. Around 25% of the genomes from high income countries were submitted within 21 days, a pattern observed in 5% of the genomes from low- and middle-income countries. We found that sequencing around 0.5% of the cases, with a turnaround time <21 days, could provide a benchmark for SARS-CoV-2 genomic surveillance. Socioeconomic inequalities undermine the global pandemic preparedness, and efforts must be made to support low- and middle-income countries improve their local sequencing capacity.

Identification of a New Endo-ß-1,4-xylanase Prospected from the Microbiota of the Termite Heterotermes tenuis.

Xylanases are hemicellulases that break down xylan to soluble pentoses. They are used for industrial purposes, such as paper whitening, beverage clarification, and biofuel production. The second-generation bioethanol production is hindered by the enzymatic hydrolysis step of the lignocellulosic biomass, due to the complex arrangement established among its constituents. Xylanases can potentially increase the production yield by improving the action of the cellulolytic enzyme complex. We prospected endo-ß-1,4-xylanases from meta-transcriptomes of the termite Heterotermes tenuis. In silico structural characterization and functional analysis of an endo-ß-1,4-xylanase from a symbiotic protist of H. tenuis indicate two active sites and a substrate-binding groove needed for the catalytic activity. No N-glycosylation sites were found. This endo-ß-1,4-xylanase was recombinantly expressed in Pichia pastoris and Escherichia coli cells, presenting a molecular mass of approximately 20 kDa. Enzymatic activity assay using recombinant endo-ß-1,4-xylanase was also performed on 1% xylan agar stained with Congo red at 30 °C and 40 °C. The enzyme expressed in both systems was able to hydrolyze the substrate xylan, becoming a promising candidate for further analysis aiming to determine its potential for application in industrial xylan degradation processes.