A Unique Enoxaparin Derived from Bovine Intestinal Heparin: A Single Purification Step of the Starting Material Assures a Bovine Enoxaparin Like the Standard from Porcine Origin.

Low-molecular-weight heparin represent a significant advancement in anticoagulant therapy with enoxaparin being a prominent example obtained exclusively through the fragmentation of porcine intestinal heparin. However, escalating demand and limited resources have raised concerns about enoxaparin supplementation. The current challenge involves exploring alternative heparin sources for large-scale enoxaparin production with bovine intestinal heparin emerging as a promising option. Our study demonstrates that enoxaparin derived from the available bovine heparin preparation differs significantly from the reference compound. Yet, the implementation of a straightforward purification step yields a preparation termed "high-anticoagulant bovine heparin". Fragmentation of this purified product through ß-elimination produces enoxaparin akin to the standard from a porcine origin. To ensure physicochemical similarity, we employed various spectroscopic, enzymatic, and chromatographic tests to compare the new bovine-derived enoxaparin with the original porcine compound. Biological activity was confirmed through in vitro coagulation assays and assessments using an animal model of venous thrombosis. Our study affirms that the ß-elimination reaction cleaves the bovine heparin chain without preferential breaks in regions with different sulfation patterns. Additionally, we scrutinized decasaccharides purified from enoxaparin preparations, providing a comprehensive demonstration of the similarity between products obtained from porcine and bovine heparin. In summary, our findings indicate that an enoxaparin equivalent to the original porcine-derived product can be derived from bovine heparin, given that the starting material undergoes a simple purification step.

Glucagon-like Peptide-1 Receptor Agonists-A Potential New Medication for Pediatric Metabolic-Dysfunction-Associated Steatotic Liver Disease (MASLD).

Metabolic-dysfunction-associated steatotic liver disease (MASLD) is the most common liver disease in children in the US and, if untreated, may progress to end-stage liver disease. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown improvement in MASLD markers in adults with type 2 diabetes mellitus (T2DM). Currently, there is a lack of medications available for the treatment of pediatric MASLD. We aimed to provide preliminary data on the effects of GLP-1 RAs on markers of MASLD in a retrospective study, in an effort to bridge this gap in the pharmacotherapies available. Nine patients from a T2DM clinic who met the following inclusion criteria were included in this study: patients diagnosed with pre-diabetes or T2DM, prescribed a GLP-1 RA in the prior 12 months, and having alanine aminotransferase (ALT) elevated to twice the upper limit of the normal range, indicating evidence of MASLD. The average change between baseline and the first measurement after starting a GLP-1 RA was calculated for ALT, hemoglobin A1c, and BMI. ALT decreased by an average of 98 points. A1c decreased by an average of 2.2 points. BMI decreased by an average of 2.4 points. There was greater reduction in ALT and A1c compared to BMI, suggesting that improvement in MASLD may be independent of weight loss. This is a preliminary study that shows potential, and prospective studies are needed to evaluate the effects of GLP-1 RAs in the management of pediatric MASLD.

Association between psychological factors and molar-incisor hypomineralization: A cross-sectional study.

BACKGROUND: Molar-incisor hypomineralization (MIH) is a developmental enamel defect characterized by opacities from white to brownish color. A suspected multifactorial etiology has been suggested, whereas psychological factors during pregnancy have only been limitedly analyzed. AIM: We assessed the association between stress, depression, and anxiety in pregnancy and the presence of MIH in children at a later age. DESIGN: Using a cross-sectional Web-based questionnaire, we included 384 mothers who had children aged 6 and 12 years from Pasto, Colombia. Data were collected between October 2021 and March 2022. Sociodemographic variables; maternal and child factors related to prenatal, natal, or postnatal problems; and psychological factors such as stress and symptoms of anxiety and depression in pregnancy were inquired. Utilizing photographs depicting MIH lesions, mothers assessed their child's MIH status. A directed acyclic graph (DAG) analysis was performed to create causal assumptions, and logistic regression models were estimated to evaluate these assumptions. p-value was set at p < .05. RESULTS: The prevalence of MIH was 33.3%; 12.8% of the participants exhibited hypomineralization in both molars and incisors. DAG analysis and logistic regression models determined that MIH (present or not) was associated with symptoms of maternal depression (ORadj = 3.26, 95% CI: 1.92-5.52, p < .001), and MIH (both molars and incisors) was associated with symptoms of maternal anxiety (ORadj = 3.49, 95% CI: 1.80-6.76, p < .001). CONCLUSION: Psychological factors, among others, were significantly associated with the presence of MIH.

The Impact and Burden of Dietary Sugars on the Liver.

NAFLD, or metabolic dysfunction-associated steatotic liver disease, has increased in prevalence hand in hand with the rise in obesity and increased free sugars in the food supply. The causes of NAFLD are genetic in origin combined with environmental drivers of the disease phenotype. Dietary intake of added sugars has been shown to have a major role in the phenotypic onset and progression of the disease. Simple sugars are key drivers of steatosis, likely through fueling de novo lipogenesis, the conversion of excess carbohydrates into fatty acids, but also appear to upregulate lipogenic metabolism and trigger hyperinsulinemia, another driver. NAFLD carries a clinical burden as it is associated with obesity, type 2 diabetes, metabolic syndrome, and cardiovascular disease. Patient quality of life is also impacted, and there is an enormous economic burden due to healthcare use, which is likely to increase in the coming years. This review aims to discuss the role of dietary sugar in NAFLD pathogenesis, the health and economic burden, and the promising potential of sugar reduction to improve health outcomes for patients with this chronic liver disease.

Approaches to Assure Similarity between Pharmaceutical Heparins from Two Different Manufacturers.

Pharmaceutical heparins from different manufacturers may present heterogeneities due to particular extraction and purification procedures or even variations in the raw material manipulation. Heparins obtained from different tissues also differ in their structure and activity. Nevertheless, there is an increased demand for more accurate assessments to ensure the similarities of pharmaceutical heparins. We propose an approach to accurately assess the similarity of these pharmaceutical preparations based on well-defined criteria, which are verified with a variety of refined analytical methods. We evaluate six commercial batches from two different manufacturers which were formulated with Brazilian or Chinese active pharmaceutical ingredients. Biochemical and spectroscopic methods and analysis based on digestion with heparinases were employed to evaluate the purity and structure of the heparins. Specific assays were employed to evaluate the biological activity. We observed minor but significant differences between the constitutive units of the heparins from these two manufacturers, such as the content of N-acetylated α-glucosamine. They also have minor differences in their molecular masses. These physicochemical differences have no impact on the anticoagulant activity but can indicate particularities on their manufacturing processes. The protocol we propose here for analyzing the similarity of unfractionated heparins is analogous to those successfully employed to compare low-molecular-weight heparins.

Urine soluble triggering receptor expressed on myeloid cells-1 is a novel biomarker for active lupus nephritis: a case-control study.

OBJECTIVES: To determine the value of plasma and urine sTREM-1 levels as a biomarker of lupus nephritis (LN) as well as extra-renal systemic lupus erythematosus (SLE). METHODS: Consecutive adult patients with SLE attending a tertiary lupus clinic in 2016-2018 were prospectively divided into 3 groups according to SLEDAI-2K and renal-SLEDAI scores: active renal lupus (ARL), active non-renal lupus (ANL), and inactive lupus (IL). Blood and spot urine samples from each group and matched healthy subjects were analysed by means of ELISA for plasma and urine sTREM-1 levels. RESULTS: The cohort included 59 patients (mean age 41.5+2.9 years, 85% female) with SLE: 15 ARL, 14 ANL, and 30 IL. The ARL group had higher scores on the SLEDAI-2K and renal-SLEDAI, and higher urine protein/creatinine ratio than the other patient groups (p=0.0001 for all). Plasma sTREM-1 level was highest in the ANL group (p=0.0085). Urine sTREM-1 level was higher in the whole SLE cohort than the healthy controls (p=0.0249), and higher in the ARL group than the others (p=0.0044). Neither plasma nor urine sTREM-1 level was associated with non-renal SLE features. On Spearman correlation analysis, urine sTREM-1 level, but not plasma sTREM-1 level, was correlated positively with renal-SLEDAI score (r=0.34, p=0.018), inversely with serum C3 and C4 levels (r=-0.42, p=0.0027 and r=-0.28, p=0.056, respectively), and positively with proteinuria (UPCR: r=0.32, p=0.0305). CONCLUSIONS: Urine sTREM-1 might serve as a potential biomarker of active renal SLE.

Anticoagulant Activity of Heparins from Different Animal Sources are Driven by a Synergistic Combination of Physical-chemical Factors.

Heparin has already been found in a variety of animal tissues but only few of them became effective sources for production of pharmaceutical preparations. Here, we correlate physical-chemical features and anticoagulant activities of structurally similar heparins employed in the past (from bovine lung, HBL), in the present (from porcine intestine, HPI) and in development for future use (from ovine intestine, HOI). Although they indeed have similar composition, our physical-chemical analyses with different chromatography and spectrometric techniques show that both HOI and HBL have molecular size notably lower than HPI and that the proportions of some of their minor saccharide components can vary substantially. Measurements of anticoagulant activities with anti-FIIa and anti-FXa assays confirmed that HPI and HOI have potency similar each other but significantly higher than HBL. Such a lower activity of HBL has been attributed to its reduced molecular size. Considering that HOI also has reduced molecular size, we find that its increased anticoagulant potency might result from an improved affinity to antithrombin (three times higher than HBL) promoted by the high content of N ,3,6-trisulfated glucosamine units, which in turn are directly involved in the heparin-antithrombin binding. Therefore, the anticoagulant activity of different heparins is driven by a balance between different physical-chemical components, especially molecular size and fine-tuning composition. Although such minor but relevant chemical differences reinforce the concept that heparins from different animal sources should indeed be considered as distinct drugs, HOI could be approved for interchangeable use with the gold standard HPI and as a suitable start material for producing new LMWHs.

Pharmacokinetic, Hemostatic, and Anticancer Properties of a Low-Anticoagulant Bovine Heparin.

Heparin is a centennial anticoagulant drug broadly employed for treatment and prophylaxis of thromboembolic conditions. Although unfractionated heparin (UFH) has already been shown to have remarkable pharmacological potential for treating a variety of diseases unrelated with thromboembolism, including cancer, atherosclerosis, inflammation, and virus infections, its high anticoagulant potency makes the doses necessary to exert non-hemostatic effects unsafe due to an elevated bleeding risk. Our group recently developed a new low-anticoagulant bovine heparin (LABH) bearing the same disaccharide building blocks of the UFH gold standard sourced from porcine mucosa (HPI) but with anticoagulant potency approximately 85% lower (approximately 25 and 180 Heparin International Units [IU]/mg). In the present work, we investigated the pharmacokinetics profile, bleeding potential, and anticancer properties of LABH administered subcutaneous into mice. LABH showed pharmacokinetics profile similar to HPI but different from the low-molecular weight heparin (LMWH) enoxaparin and diminished bleeding potential, even at high doses. Subcutaneous treatment with LABH delays the early progression of Lewis lung carcinoma, improves survival, and brings beneficial health outcomes to the mice, without the advent of adverse effects (hemorrhage/mortality) seen in the animals treated with HPI. These results demonstrate that LABH is a promising candidate for prospecting new therapeutic uses for UFH.

Sarcopenia as a Predictor of Survival in Patients with Pancreatic Adenocarcinoma After Pancreatectomy.

OBJECTIVE: To determine whether sarcopenia can potentially predict worse survival after resection of pancreatic ductal adenocarcinoma. BACKGROUND: Sarcopenia is correlated with poor outcomes in hepatopancreatobiliary malignancies, but the relationship of both its qualitative and quantitative features with patient survival after pancreatectomy has not been investigated in a western population. PATIENTS AND METHODS: Preoperative cross-sectional computed tomography scans of consecutive patients who underwent pancreatectomy in 2005-2017 were evaluated for skeletal muscle index (SMI), intramuscular adipose tissue content (IMAC), and visceral-to-subcutaneous adipose tissue area ratio (VSR). Sex-specific categorical cut-offs were determined. Findings were correlated with outcome. RESULTS: The study included 111 patients, 47% of whom were female, with a median age of 67 years (range: 35-87 years), and median body mass index of 23 kg/m2 (range: 16-40 kg/m2); 77% had a Whipple procedure and 66% received adjuvant chemotherapy. Low SMI correlated with poor overall survival (OS) (P = 0.007), disease-specific survival (DSS) (P = 0.006), and recurrence-free survival (RFS) (P = 0.01). High IMAC correlated with poor OS (P = 0.04). Patients with high IMAC tended to have a shorter DSS (P = 0.09), with no correlation with RFS (P = 0.6). VSR was not associated with survival. Multivariable analysis yielded an independent association of low SMI with OS (HR = 1.7, 95%CI: 1.1-2.8, P = 0.02), DSS (HR = 1.8, 95%CI: 1.03-3.2, P = 0.04), and RFS (HR = 1.8, 95%CI: 1.1-2.8, P = 0.01), and of high IMAC with OS (HR = 1.9, 95%CI: 1.1-3.1, P = 0.01). CONCLUSION: Both qualitative and quantitative measures of skeletal muscle were independently associated with impaired survival in patients with resectable PDAC. Sarcopenia might serve as an early radiographic surrogate of aggressive tumor behavior, with potential implications for clinical decision-making and future study.

Neutrophil-to-Lymphocyte Ratio Predicts Recurrence Pattern in Patients with Resectable Colorectal Liver Metastases.

BACKGROUND: Studies have suggested that neutrophil-to-lymphocyte ratio (NLR) has value as a predictor of long-term outcomes in various cancer types. Its prognostic potential in patients with CRLM has not been thoroughly investigated. This original, retrospective study assessed the relationship between the preoperative NLR, survival outcomes, and recurrence patterns in patients after colorectal liver metastasis resection (CRLM). METHODS: The prospectively maintained database of a tertiary medical center was queried for all patients who underwent CRLM resection between 2005 and 2017. Patients were divided into two groups: NLR <3 (normal) or >3 (high). Recurrence risk was analysed using Fine and Gray correction for competing risk method and cause specific analyses. RESULTS: The cohort included 231 patients of whom 53 (23%) had a high neutrophil-to-lymphocyte ratio. At presentation, 35% had synchronous disease and 48% had a solitary metastasis; median tumor size was 2 cm. Patients with a high NLR had a significantly higher rate of simultaneous colorectal resection (P = 0.01). A high NLR was independently associated with worse OS (P = 0.02), worse DFS (P = 0.03), and higher risk of recurrence (P = 0.048), specifically recurrence with an extrahepatic pattern (P = 0.03). CONCLUSIONS: A high preoperative NLR was independently associated with poorer survival outcomes and extrahepatic recurrence pattern. The NLR appears to have prognostic importance in CRLM and may serve as a surrogate marker of aggressive systemic disease after resection. These findings warrant external validation, preferably in a prospective design.

Narrative medicine: Re-engaging and re-energizing ourselves through story.

Physicians and other allied health professionals have many distractions from their work and from original motivations to become health caring professionals. Activities that detract from making meaningful connection with patients result in high levels of work dissatisfaction and burnout even at early stages of career or training. Narrative Medicine provides an antidote to these influences. It is an experiential discipline that draws on the Arts and Humanities, connects health professionals to their original motivation to care, cultivates the ability to engage patients and stimulates professional growth. When practiced with interdisciplinary teams, commonalities and mutual purpose are highlighted, promoting group cohesion and appreciation. The practice of this discipline and development of narrative competence relates closely to the advancement along numerous milestones, particularly Patient Care, Interpersonal and Communication Skills, and Professionalism. This article describes an experiential and didactic workshop presented at the 2019 Forum for Behavioral Science in Family Medicine which outlined a Narrative Medicine curriculum as taught at a community hospital Family Medicine residency. The curriculum is aimed at promoting residents' professional development, personal wellbeing, and capacity to engage patients.

Effect of Mineral Aggregates and Chemical Admixtures as Internal Curing Agents on the Mechanical Properties and Durability of High-Performance Concrete.

In the present work, the effect of mineral aggregates (pumice stone and expanded clay aggregates) and chemical admixtures (superplasticizers and shrinkage reducing additives) as an alternative internal curing technique was investigated, to improve the properties of high-performance concrete. In the fresh and hardened state, concretes with partial replacements of Portland cement (CPC30R and OPC40C) by pulverized fly ash in combination with the addition of mineral aggregates and chemical admixtures were studied. The physical, mechanical, and durability properties in terms of slump, density, porosity, compressive strength, and permeability to chloride ions were respectively determined. The microstructural analysis was carried out by scanning electronic microscopy. The results highlight the effect of the addition of expanded clay aggregate on the internal curing of the concrete, which allowed developing the maximum compressive strength at 28 days (61 MPa). Meanwhile, the replacement of fine aggregate by 20% of pumice stone allowed developing the maximum compressive strength (52 MPa) in an OPC-based concrete at 180 days. The effectiveness of internal curing to develop higher strength is attributed to control in the porosity and a high water release at a later age. Finally, the lowest permeability value at 90 days (945 C) was found by the substitutions of fine aggregate by 20% of pumice stone saturated with shrinkage reducing admixture into pores and OPC40C by 15% of pulverized fly ash. It might be due to impeded diffusion of chloride ions into cement paste in the vicinity of pulverized fly ash, where the pozzolanic reaction has occurred. The proposed internal curing technology can be considered a real alternative to achieve the expected performance of a high-performance concrete since a concrete with a compressive strength range from 45 to 67 MPa, density range from 2130 to 2310 kg/m3, and exceptional durability (< 2000 C) was effectively developed.

Polysaccharide composition of an anticoagulant fraction from the aqueous extract of Marsypianthes chamaedrys (Lamiaceae).

Marsypianthes chamaedrys (Lamiaceae) is a medicinal plant popularly used against envenomation by snakebite. Pharmacological studies have shown that extracts of M. chamaedrys have antiophidic, anti-inflammatory and anticoagulant properties, supporting the ethnopharmacological use. In this study, an aqueous extract of aerial parts of M. chamaedrys showed anticoagulant activity in the activated partial thromboplastin time assay (0.54 IU/mg). The bioassay-guided fractionation using ethanol precipitation and gel filtration chromatography on Sephadex G-50 and Sephadex G-25 resulted in a water-soluble fraction with increased anticoagulant activity (Fraction F2-A; 2.94 IU/mg). A positive correlation was found between the amount of uronic acids and the anticoagulant potential of the active samples. Chemical and spectroscopic analyses indicated that F2-A contained homogalacturonan, type I rhamnogalacturonan, type II arabinogalactan and α-glucan. UV and FT-IR spectra indicated the possible presence of ferulic acid. Pectic polysaccharides and type II arabinogalactans may be contributing to the anticoagulant activity of the aqueous extract of M. chamaedrys in the APTT assay.

A rare case of Takotsubo syndrome in a patient 5 months after heart transplantation.

Takotsubo syndrome is an acute heart failure syndrome with a pathogenesis that is attributed to sympathetic stimulation. This case report describes a unique case of a 5 month heart-transplanted female patient who developed apical ballooning on an echocardiography exam performed following an emotional stress event. Detailed clinical investigations and imaging techniques confirmed the diagnosis of Takatsubo syndrome. Our case indicates that Takatsubo's cardiomyopathy should be included in the differential diagnosis of heart-transplanted patients presenting with sudden graft dysfunction mimicking acute graft rejection or acute coronary syndrome.

Converting the Distinct Heparins Sourced from Bovine or Porcine Mucosa into a Single Anticoagulant Drug.

Unfractionated heparin (UFH) and their low-molecular-weight derivatives are sourced almost exclusively from porcine mucosa (HPI); however, a worldwide introduction of UFH from bovine mucosa (HBI) has been recommended to reinforce the currently unsteady supply chain of heparin products. Although HBI has different chemical composition and about half of the anticoagulant potency of HPI (∼100 and ∼180 international unit [IU]/mg, respectively), they have been employed as interchangeable UFHs in some countries since the 1990s. However, their use as a single drug provoked several bleeding incidents in Brazil, which precipitated the publication of the first monographs exclusive for HBI and HPI by the Brazilian Pharmacopoeia. Nevertheless, we succeed in producing with high-resolution anion-exchange chromatography a novel HBI derivative with anticoagulant potency (200 IU/mg), disaccharide composition (enriched in N,6-disulfated α-glucosamine) and safety profile (bleeding and heparin-induced thrombocytopaenia potentials and protamine neutralization) similar to those seen in the gold standard HPI. Therefore, we show that it is possible to equalize the composition and pharmacological characteristics of these distinct UFHs by employing an easily implementable improvement in the HBI manufacturing.

Heparins Sourced From Bovine and Porcine Mucosa Gain Exclusive Monographs in the Brazilian Pharmacopeia.

Most of the unfractionated heparin (UFH) consumed worldwide is manufactured using porcine mucosa as raw material (HPI); however, some countries also employ products sourced from bovine mucosa (HBI) as interchangeable versions of the gold standard HPI. Although accounted as a single UFH, HBI, and HPI have differing anticoagulant activities (~100 and 200 IU mg-1, respectively) because of their compositional dissimilarities. The concomitant use of HBI and HPI in Brazil had already provoked serious bleeding incidents, which led to the withdrawal of HBI products in 2009. In 2010, the Brazilian Pharmacopeia (BP) formed a special committee to develop two complementary monographs approaching HBI and HPI separately, as distinct active pharmaceutical ingredients (APIs). The committee has rapidly agreed on requirements concerning the composition and presence of contaminants based on nuclear magnetic resonance and anion-exchange chromatography. On the other hand, consensus on the anticoagulant activity of HBI was the subject of long and intense discussions. Nevertheless, the committee has ultimately agreed to recommend minimum anti-FIIa activities of 100 IU mg-1 for HBI and 180 IU mg-1 for HPI. Upon the approval by the Brazilian Health Authority (ANVISA), the BP published the new monographs for HPI and HBI APIs in 2016 and 2017, respectively. These pioneer monographs represent a pivotal step toward the safest use of HBI and HPI as interchangeable anticoagulants and serve as a valuable template for the reformulation of pharmacopeias of other countries willing to introduce HBI.

Optimization of the integral valorization process for orange peel waste using a design of experiments approach: Production of high-quality pectin and activated carbon.

The aim of this study was to optimize the integral valorization of orange peel waste by obtaining activated carbon after a process of pectin recovery in recycling of orange peel by transformation to value-added products of pectin extraction and activated carbon preparation. The study was supported by statistical analysis, and the significant factors and optimal conditions were obtained from the statistical analysis. Using a representative sample of orange peel waste, a yield of 29.37% pectin was recovered at the optimal operating conditions (phosphoric acid as the extraction agent, 95 °C as the impregnation temperature and a 2-hour extraction time). Activated carbon (AC) was prepared from the remaining solid residue. The conditions that improve the resulting material quality were H3PO4 [0.6 M] used as the activating agent, an impregnation temperature of 95 °C, a carbonization temperature of 400 °C and 1 h of carbonization time. The obtained AC showed a sorption capacity of 2342.91 mg g-1, a value higher than that reported for commercial activated carbon. Using a model dye chemical, the sorption kinetics and thermodynamics of AC were found to follow a pseudo-second-order rate and the Freundlich models, respectively. Using the process conditions obtained in this study, it was possible to optimize the yield and also obtain good-quality products from valorization of orange peel.

Molecular characteristics of polysulfated fractions from the green seaweed Caulerpa cupressoides and actions on thrombin generation in vitro

Caulerpa cupressoides produces sulfated polysaccharides (Cc-SPs) with serpin-dependent anticoagulant effect, but their actions on thrombin generation (TG) are unknown. This study aimed to partially characterize Cc-SPs and examine their potential as modulators of TG. Infrared analysis characterized extract containing three ulvan fractions (Cc-SP1, -SP2 and -SP3) separated by DEAEcellulose chromatography, with differences in the relative proportions of sulfate (10.99-18.38%) and total sugars (46.59-51.12%), without presenting proteins. Charge density patterns and nonSPs varying from 8 to > 100 kDa on agarose and polyacrylamide gel electrophoresis by sequential staining with toluidine blue and stains-all were also confirmed by gel permeation chromatography. The molecular weight of Cc-SP2 was not altered after treatment with 0.4 M HCl up to 5 h. Only Cc-SP2 altered the activated partial thromboplastin time (15 ± 0.3 IU) vs. heparin (193 IU) and abolished at high concentrations (> 4.1 μg) TG by intrinsic pathway in 60-fold diluted human plasma, while at 4.1 μg attenuated TG by 33.87% delaying the lag phase (32 min.) vs. control (28 min.). Cc-SP2 induced concentration-dependent TG in system without cephalin. Heparin abolished TG at 4.15-fold lower amount, but did not stimulate TG. Therefore, Cc-SPs express dual effects on thrombosis in vitro.

Imminent risk of a global shortage of heparin caused by the African Swine Fever afflicting the Chinese pig herd.

Most of the unfractionated and low-molecular-weight heparins available worldwide are produced by Chinese companies from porcine mucosa. China is the world's largest producer of pork and thus has plenty of raw material to produce heparins. However, the deadly African Swine Fever (ASF) outbreaks afflicting China since August 2018 may cause extensive losses to the pig herd, with serious consequences for the global supply of heparins. In 2008, a sudden shortage of heparin's raw material resulting from a viral disease in Chinese pigs prompted adulterations responsible for 80 deaths and hundreds of adverse events. This incident revealed the fragility of such a supply chain, which is mostly based on raw material from a single animal from a single country. A worldwide introduction of bovine mucosa heparins manufactured in different countries certainly is a feasible way to mitigate eventual shortages of these life-saving anticoagulants caused by local veterinary problems such as the ASF threatening China now.

Effect of Rotary Instrument Mineral Oil Lubricant on Osseointegration: A Randomized, Blinded Study in Rabbits.

The mechanisms of early failures in dental implant osseointegration are unclear. A possible cause of low levels of bone formation is lubricant contamination on implants during insertion. To explore the impact of lubricant contamination on dental implants, we used 5 New Zealand rabbits and inserted 2 implants per tibia in each animal for a total of 4 implants per animal (20 implants in total). In general, bicorticalization was achieved. The first implant was placed as suggested by the manufacturer with no lubricant used (control). The second implant was placed using a freshly lubricated contra-angle handpiece, which was used only for the test implants. Implant allocation was randomized, and the examining histologist was blinded to the results. All implants were placed by the same surgeon. The animals were maintained in accordance with animal experimentation guidelines. None of the implants failed to osseointegrate. Moreover, no significant difference was observed between the test and control groups. Based on the results of this study, the use of rotary instrument mineral oil lubricant did not jeopardize the osseointegration of dental implants in New Zealand rabbits.