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McClellan Hayes posted an update 2 weeks, 4 days ago
In vivo ES-2 xenograft model showed PAS+/CD31- VM structures (staining positive for both SORT1 and CD133). TH1904, a Doxorubicin-peptide conjugate that is internalized by SORT1, significantly decreased in vitro VM at low nM concentrations. In contrast, VM was unaffected by unconjugated Doxorubicin or Doxil (liposomal Doxorubicin) up to μM concentrations. TH1902, a Docetaxel-peptide conjugate, altered even more efficiently in vitro VM at pM concentrations. Overall, current data evidence for the first time that 1) SORT1 itself exerts a crucial role in both ES-2 and MDA-MB-231 VM, and that 2) VM in these cancer cell models can be efficiently inhibited by the peptide-drug conjugates TH1902/TH1904. These new findings also indicate that both peptide-drug conjugates, in addition to their reported cytotoxicity, could possibly inhibit VM in SORT1-positive TNBC and ovarian cancer patients.
Children commonly present in diabetic ketoacidosis (DKA) secondary to Type 1 diabetes mellitus. Electrolyte imbalances and cerebral edema are common complications in the pediatric age group; however, patients may also have additional metabolic disturbances such as hyperlipidemia. We report a case of a pediatric patient with new-onset type 1 Diabetes Mellitus (DM) and DKA complicated by severe hypertriglyceridemia with recent exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
A three-year-old male noted to be SARS-CoV-2 positive, presented with hyperglycemia, metabolic acidosis, and ketosis consistent with DKA. Patient was later found to have severe hypertriglyceridemia (greater than 5680 mg/dL). He was managed with intravenous (IV) fluids and IV insulin replacement with improvement of triglycerides.
Severe hypertriglyceridemia in DKA, though rare in the pediatric population, responds very well to IV insulin therapy. This case also highlights possible need for early lipid screening in DKA patients with SARS-CoV-2 positive status.
Severe hypertriglyceridemia in DKA, though rare in the pediatric population, responds very well to IV insulin therapy. This case also highlights possible need for early lipid screening in DKA patients with SARS-CoV-2 positive status.
During an epidemic, screening processes can play a crucial role in limiting the spread of the infection. ML323 The aim of this study was to describe the epidemiological profile of COVID-19 suspected cases and to evaluate the performance of the triage process in predicting COVID-19 in Southern Tunisia.
It was a prospective study including all patients consulting to the Hedi Chaker University Hospital departments from March to June 2020. A clinical triage score (CTS) was used to assess the risk of the infection and to refer patients to the appropriate part of the facility accordingly.
Overall, 862 patients were enrolled, among whom 505 patients (58.6%) were classified as suspected cases (CTS ≥4). Of these, 46.9% (n = 237) were of mild form. Samples were collected from 215 patients (24.9%), among whom five were COVID-19 positive, representing a positive rate of 2.3%. The in-hospital cumulative incidence rate of COVID-19 was 580/100000 patients. The total daily incidence decreased significantly during the study period (p < 0.001, chi-square for linear trend = 25.6). At a cut-off of four, the CTS had a sensitivity of 40%, a specificity of 32.4%, and negative and positive predictive values of 95.8% and 1.4%, respectively.
Although the triage process based on the CTS was not as performant as the RT-PCR, it was crucial to interrupt virus spread among hospitalized patients in “COVID-19-free departments”.
Although the triage process based on the CTS was not as performant as the RT-PCR, it was crucial to interrupt virus spread among hospitalized patients in “COVID-19-free departments”.The COVID-19 pandemic has made transportation hubs vulnerable to public health risks. In response, policies using nonpharmaceutical interventions have been implemented, changing the way individuals interact within these facilities. However, the impact of building design and operation on policy efficacy is not fully discovered, making it critical to investigate how these policies are perceived and complied in different building spaces. Therefore, we investigate the spatial drivers of user perceptions and policy compliance in airports. Using text mining, we analyze 103,428 Google Maps reviews of 64 major hub airports in the US to identify representative topics of passenger concerns in airports (i.e., Staff, Shop, Space, and Service). Our results show that passengers express having positive experiences with Staff and Shop, but neutral or negative experiences with Service and Space, which indicates how building design has impacted policy compliance and the vulnerability of health crises. Furthermore, we discuss the actual review comments with respect to 1) spatial design and planning, 2) gate assignment and operation, 3) airport service policy, and 4) building maintenance, which will construct the foundational knowledge to improve the resilience of transportation hubs to future health crises.The 2020 Covid-19 pandemic provides an empirical testing ground for assessing the impact of critical events on societal transitions. Such events are typically seen as exogenous to the transition process, an assumption which is investigated in this paper. Using a qualitative system dynamics modelling approach we conceptualize transition pathways as sets of interacting sequences of events. This enables the analysis of event sequences that constitute the evolving pandemic as impacting on those pathways. We apply this approach to the provision of (auto)mobility and food in the UK. This shows the way in which the pandemic has had a differential effect on ongoing transitions in both systems, sometimes slowing them down, and sometimes accelerating them. In addition, it reveals how it has established new transition pathways. The empirical work further shows how qualitative modelling with system dynamics facilitates an explicit and systematic comparative analysis of transition case studies.Inductively coupled plasma mass spectrometry (ICP-MS) analytical method was used to determine the content of 40 elements in 38 soybean samples (Glycine Max) from 4 countries. Multivariate statistical methods, such as principal components analysis (PCA), were performed to analyze the obtained data to establish the provenance of the soybeans. Although soybean is widely marketed in many countries, no universal method is used to discriminate the origin of these cereals. Our study introduced the initial step to the identification of the geographical origin of commercial soybean marketed in Vietnam. The analysis pointed out that there are significant differences in the mean of 33 of the 40 analyzed elements among 4 countries’ soybean samples, namely, 11B, 27Al, 44Ca, 45Sc, 47Ti, 55Mn, 56Fe, 59Co, 60Ni, 63Cu, 66Zn, 69Ga, 75As, 78Se, 85Rb, 88Sr, 89Y, 90Zr, 93Nb, 95Mo, 103Rh, 137Ba, 163Dy, 165Ho, 175Lu, 178Hf, 181Ta, 182W, 185Re, 197Au, 202Hg, 205Tl, and 208Pb. The PCA analysis showed that the soybean samples can be classified correctly according to their original locations. This research can be used as a prerequisite for future studies of using the combination of elemental composition analysis with statistical classification methods for an accurate provenance establishment of soybean, which determined a variation of key markers for the original discrimination of soybean.Granulomatosis with polyangiitis (GPA) typically presents with upper or lower respiratory tract symptoms and/or with renal involvement. Although it can affect the peripheral nervous system frequently, with mononeuritis multiplex being the most common pattern, the occurrence of peripheral sensory-motor polyneuropathy as a presenting manifestation is distinctly rare. Prevalence of digital gangrene is also extremely rare in GPA. We describe a 46-year-old woman presenting with severe peripheral sensorimotor polyneuropathy affecting bilateral lower limbs preceded by a purpuric skin rash and multiple painful ulcers confined to the lower limbs. She had evidence of digital ischemia affecting multiple toes and dry gangrene of the left 4th toe. Diagnosis of GPA was made based on skin biopsy, positive ANCA serology, and clinical criteria. She made a good recovery following aggressive immunosuppressive treatment with methylprednisolone and cyclophosphamide and was maintained on prednisolone and azathioprine. This case highlights the importance of suspecting GPA in a patient presenting with sensorimotor polyneuropathy and/or digital ischemia even in the absence of more classic presenting features and underlies the necessity of accurate differential diagnosis in evaluating a case of peripheral neuropathy.
Acute kidney injury (AKI) is a common and important complication of coronavirus disease 2019 (COVID-19). Further characterization is required to reduce both short- and long-term adverse outcomes.
We examined registry data including adults with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection admitted to five London Hospitals from 1 January to 14 May 2020. Prior end-stage kidney disease was excluded. Early AKI was defined by Kidney Disease Improving Global Outcomes creatinine criteria within 7 days of admission. Independent associations of AKI and survival were examined in multivariable analysis. Results are given as odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals.
Among 1855 admissions, 455 patients (24.5%) developed early AKI 200 (44.0%) Stage 1, 90 (19.8%) Stage 2 and 165 (36.3%) Stage 3 (74 receiving renal replacement therapy). The strongest risk factor for AKI was high C-reactive protein [OR 3.35 (2.53-4.47), P < 0.001]. Death within 30 days occurred in 242 (53.2%) with AKI compared with 255 (18.2%) without. In multivariable analysis, increasing severity of AKI was incrementally associated with higher mortality Stage 3 [HR 3.93 (3.04-5.08), P < 0.001]. In 333 patients with AKI surviving to Day 7, 134 (40.2%) recovered, 47 (14.1%) recovered then relapsed and 152 (45.6%) had persistent AKI at Day 7; an additional 105 (8.2%) patients developed AKI after Day 7. Persistent AKI was strongly associated with adjusted mortality at 90 days [OR 7.57 (4.50-12.89), P < 0.001].
AKI affected one in four hospital in-patients with COVID-19 and significantly increased mortality. Timing and recovery of COVID-19 AKI is a key determinant of outcome.
AKI affected one in four hospital in-patients with COVID-19 and significantly increased mortality. Timing and recovery of COVID-19 AKI is a key determinant of outcome.Point-of-care testing (POCT) performed by the patient at home, paired with eHealth technologies, offers a wealth of opportunities to develop individualized, empowering clinical pathways. The non-dialysis-dependent chronic kidney disease (CKD) patient who is at risk of or may already be suffering from a number of the associated complications of CKD represents an ideal patient group for the development of such initiatives. The current coronavirus disease 2019 pandemic and drive towards shielding vulnerable individuals have further highlighted the need for home testing pathways. In this narrative review we outline the evidence supporting remote patient management and the various technologies in use in the POCT setting. We then review the devices currently available for use in the home by patients in five key areas of renal medicine anaemia, biochemical, blood pressure (BP), anticoagulation and diabetes monitoring. Currently there are few devices and little evidence to support the use of home POCT in CKD. While home testing in BP, anticoagulation and diabetes monitoring is relatively well developed, the fields of anaemia and biochemical POCT are still in their infancy.