Demonstration of astrocytes in cultured amniotic fluid cells of three cases with neural-tube defect

We have investigated the origin of rapidly adhering (RA) cells in three cases of neural tube defects (two anencephali, one encephalocele). We were able to demonstrate the presence of glial fibrillary acidic (GFA) protein in variable percentages (4–80%) of RA cells cultured for 4–6 days by use of indirect immunofluorescence with GFA antiserum. Cells cultured from amniotic fluids of normal pregnancies and fetal fibroblasts were completely GFA protein negative. GFA protein is well established as a highly specific marker for astrocytes. Demonstration of astrocytes may prove to be a criterion of high diagnostic value for neural tube defects. The percentage of astrocytes decreased with increasing culture time, while the percentage of fibronectin positive cells increased both in amniotic fluid cell cultures from neural tube defects and normal pregnancies

A tree without leaves

The puzzle presented by the famous stumps of Gilboa, New York, finds a solution in the discovery of two fossil specimens that allow the entire structure of these early trees to be reconstructed

Honey can inhibit and eliminate biofilms produced by Pseudomonas aeruginosa

© 2019, The Author(s). Chronic wound treatment is becoming increasingly difficult and costly, further exacerbated when wounds become infected. Bacterial biofilms cause most chronic wound infections and are notoriously resistant to antibiotic treatments. The need for new approaches to combat polymicrobial biofilms in chronic wounds combined with the growing antimicrobial resistance crisis means that honey is being revisited as a treatment option due to its broad-spectrum antimicrobial activity and low propensity for bacterial resistance. We assessed four well-characterised New Zealand honeys, quantified for their key antibacterial components, methylglyoxal, hydrogen peroxide and sugar, for their capacity to prevent and eradicate biofilms produced by the common wound pathogen Pseudomonas aeruginosa. We demonstrate that: (1) honey used at substantially lower concentrations compared to those found in honey-based wound dressings inhibited P. aeruginosa biofilm formation and significantly reduced established biofilms; (2) the anti-biofilm effect of honey was largely driven by its sugar component; (3) cells recovered from biofilms treated with sub-inhibitory honey concentrations had slightly increased tolerance to honey; and (4) honey used at clinically obtainable concentrations completely eradicated established P. aeruginosa biofilms. These results, together with their broad antimicrobial spectrum, demonstrate that manuka honey-based wound dressings are a promising treatment for infected chronic wounds, including those with P. aeruginosa biofilms

Antibiotic-specific differences in the response of Staphylococcus aureus to treatment with antimicrobiala combined with manuka honey

Skin infections caused by antibiotic resistant Staphylococcus aureus are a significant health problem worldwide; often associated with high treatment cost and mortality rate. Complex natural products like New Zealand (NZ) manuka honey have been revisited and studied extensively as an alternative to antibiotics due to their potent broad-spectrum antimicrobial activity, and the inability to isolate honey-resistant S. aureus. Previous studies showing synergistic effects between manuka-type honeys and antibiotics have been demonstrated against the growth of one methicillin-resistant S. aureus (MRSA) strain. We have previously demonstrated strong synergistic activity between NZ manuka-type honey and rifampicin against growth and biofilm formation of multiple S. arueus strains. Here, we have expanded our investigation using multiple S. aureus strains and four different antibiotics commonly used to treat S. aureus-related skin infections: rifampicin, oxacillin, gentamicin, and clindamycin. Using checkerboard microdilution and agar diffusion assays with S. aureus strains including clinical isolates and MRSA we demonstrate that manuka-type honey combined with these four antibiotics frequently produces a synergistic effect. In some cases when synergism was not observed, there was a significant enhancement in antibiotic susceptibility. Some strains that were highly resistant to an antibiotic when present alone become sensitive to clinically achievable concentrations when combined with honey. However, not all of the S. aureus strains tested responded in the same way to these combinational treatments. Our findings support the use of NZ manuka-type honeys in clinical treatment against S. aureus-related infections and extend their potential use as an antibiotic adjuvant in combinational therapy. Our data also suggest that manuka-type honeys may not work as antibiotic adjuvants for all strains of S. aureus, and this may help determine the mechanistic processes behind honey synergy

Neonatal desensitisation for the study of regenerative medicine

Cell replacement is a therapeutic option for numerous diseases of the CNS. Current research has identified a number of potential human donor cell types, for which preclinical testing through xenotransplantation in animal models is imperative. Immune modulation is necessary to promote donor cell survival for sufficient time to assess safety and efficacy. Neonatal desensitization can promote survival of human donor cells in adult rat hosts with little impact on the health of the host and for substantially longer than conventional methods, and has subsequently been applied in a range of studies with variable outcomes. Reviewing these findings may provide insight into the method and its potential for use in preclinical studies in regenerative medicine

Association of Sodium-Glucose Cotransporter 2 Inhibitor vs Dipeptidyl Peptidase-4 Inhibitor Use With Risk of Incident Obstructive Airway Disease and Exacerbation Events Among Patients With Type 2 Diabetes in Hong Kong

Importance Patients with diabetes are at higher risk for obstructive airway disease (OAD). In recent meta-analyses of post hoc analyses of cardiorenal trials, sodium-glucose cotransporter 2 inhibitors (SGLT2Is) were suggested to reduce the risk of OAD adverse events. However, a clinical investigation of this association is warranted. Objective This study aimed to investigate the association of SGLT2I use vs dipeptidyl peptidase-4 inhibitor (DPP4I) use with OAD incidence and exacerbation events in patients with type 2 diabetes. Design, Setting, and Participants This retrospective population-based cohort study used electronic health data from a territory-wide electronic medical database in Hong Kong. Data were collected for patients with type 2 diabetes who were prescribed SGLT2Is or DPP4Is between January 1, 2015, and December 31, 2018. Patients were followed for a median of 2.2 years between January 1, 2015, and December 31, 2020. A prevalent new-user design was adopted to match patients based on previous exposure to the study drugs. Propensity score matching was used to balance baseline characteristics. Exposures Patients with type 2 diabetes using SGLT2Is (exposure of interest) or DPP4Is (active comparator). Main Outcomes and Measures The main outcomes were the first incidence of OAD and the count of OAD exacerbations. The risk of incident OAD was estimated using a Cox proportional hazards regression model. The rate of exacerbations was estimated using zero-inflated Poisson regression. Statistical analysis was performed on November 13, 2022. Results This study included 30 385 patients. The propensity score–matched non-OAD cohort (incidence analysis) consisted of 5696 SGLT2I users and 22 784 DPP4I users, while the matched OAD cohort (exacerbations analysis) comprised 381 SGLT2I users and 1524 DPP4I users. At baseline, 56% of patients in the non-OAD cohort were men and the mean (SD) age was 61.2 (9.9) years; 51% of patients in the OAD cohort were men and the mean age was 62.2 (10.8) years. Compared with DPP4I use, SGLT2I use was associated with a lower risk of incident OAD (hazard ratio, 0.65 [95% CI, 0.54-0.79]; P < .001) and a lower rate of exacerbations (rate ratio, 0.54 [95% CI, 0.36-0.83]; P = .01). The associations were consistent in sex subgroup analysis. Conclusions and Relevance The findings of this retrospective cohort study of patients with type 2 diabetes in Hong Kong suggest that SGLT2I use was associated with a reduced risk of incident OAD and a lower rate of exacerbations in a clinical setting compared with DPP4I use. These findings further suggest that SGLT2Is may provide additional protective effects against OAD for patients with type 2 diabetes and that further investigation is warranted

Lifestyle factors associated with sex differences in Kaposi sarcoma incidence among adult black South Africans: A case-control study

Kaposi Sarcoma (KS) is endemic in several countries in Southern and Eastern Africa, relatively rare worldwide but a leading cancer among people living with HIV. KS has always been more common in adult males than females. We assessed the prevalence of known cancer modifying factors (parity, hormonal contraceptive use in females, sex-partners, smoking and alcohol consumption in both sexes), and their relationship to KS, and whether any of these could account for the unequal KS sex ratios. We calculated logistic regression case-control adjusted odds ratios (ORadj), and 95% confidence intervals (95%CI), between KS and each of the modifying factors, using appropriate comparison controls. Controls were cancer types that had no known relationship to exposures of interest (infection or alcohol or smoking or contraceptive use). The majority of the 1275 KS cases were HIV positive (97%), vs. 15.7% in 10,309 controls. The risk of KS among those with HIV was high in males (ORadj=116.70;95%CI=71.35–190.88) and females (ORadj=93.91;95%CI=54.22–162.40). Among controls, the prevalence of smoking and alcohol consumption was five and three times higher in males vs. females. We found a positive association between KS and heavy vs. non-drinking (ORadj=1.31;95%CI=1.03–1.67), and in current heavy vs. never smokers (ORadj=1.82;95%CI=1.07–3.10). These associations remained positive for alcohol consumption (but with wider CIs) after stratification by sex, and restriction to HIV positive participants. We found no evidence of interactions of smoking and alcohol by sex. Smoking and alcohol consumption may provide a possible explanation for the KS sex differences, given both exposures are more common in men, but confounding and bias cannot be fully ruled out. The role smoking and alcohol play in relation to viral loads of HIV/KSHV, differences in immunological responses or other genetic differences between males and females warrant further studies

Epidemiology of Kaposi's sarcoma in sub-Saharan Africa

Kaposi's sarcoma (KS) has become a common AIDS-defining cancer in sub-Saharan Africa. Kaposi's sarcoma-associated human herpesvirus strongly modulated by HIV-related immune suppression are the principal causes of this cancer. No other risk factors have been identified as playing a strong role. HIV prevention programs and good coverage of antiretroviral therapy (ART) in developed countries resulted in a remarkable decline in HIV-KS incidence and better KS prognosis. By contrast, in sub-Saharan Africa, population ART rollout has lagged, but clinical studies have shown positive results in reduction of KS incidence and better KS prognosis. However, the effect of ART rollout in relation to population KS incidence is unclear. We describe the incidence of KS in sub-Saharan Africa, in four time-periods, (1) before 1980 (before HIV/AIDS era); (2) 1981–2000 (early HIV/AIDS era, limited or no ART coverage); (3) 2001–2010 (early ART coverage period); and (4) 2011–2016 (fair to good ART coverage period). We used KS incidence data available from WHO-International Agency for Research on Cancer (IARC) publications and the Africa Cancer Registry Network. National HIV prevalence and ART coverage data were derived from UNAIDS/WHO. A rapid increase in KS incidence was observed throughout sub-Saharan Africa as the HIV epidemic progressed, reaching peak incidences in Period 2 (pre-ART rollout) of 50.8 in males and 20.3 per 100 000 in females (Zimbabwe, Harare). The overall unweighted average decline in KS incidence between 2000 and 2010 and 2011–2016 was 27%, but this decline was not statistically significant across the region. ART rollout coincides with a decline in KS incidence across several regions in sub-Saharan Africa. The importance of other risk factors such as reductions in HIV incidence could not be ascertained

Kaposi sarcoma-associated herpesvirus, HIV-1 and Kaposi sarcoma risk in black South Africans diagnosed with cancer during antiretroviral treatment rollout

Kaposi sarcoma-associated herpesvirus (KSHV) causes Kaposi sarcoma (KS). The risk of KS is amplified in HIV-immunosuppressed individuals and antiretroviral therapy (ART) reduces KS incidence. Reliable data on the relationship between these factors are lacking in Africa. We used questionnaires and serum from 7886 black South Africans (18-74 years) with incident cancer, recruited between 1995 and 2016. ART rollout started in 2004. We measured associations between KS, HIV-1 and KSHV before and after ART rollout. We measured seropositivity to HIV-1, KSHV latency-associated nuclear antigen (LANA) and glycoprotein (K8.1) and calculated case-control-adjusted odds ratios (ORadj) and 95% confidence intervals (CI) in relation to KS and KSHV infection, before (1995-2004), early (2005-2009) and late (2010-2016) ART rollout periods. KSHV seropositivity among 1237 KS cases was 98%. Among 6649 controls, KSHV seropositivity was higher in males (ORadj = 1.4 [95%CI 1.23-1.52]), in persons with HIV, (ORadj = 4.2 [95%CI 3.74-4.73]) and lower in high school leavers (ORadj = 0.7 [95%CI 0.59-0.83]). KSHV seropositivity declined over the three ART rollout periods (37%, 28% and 28%, Ptrend <.001) coinciding with increases in high school leavers over the same periods (46%, 58% and 67%, Ptrend <.001). HIV-1 seroprevalence increased from 10% in the pre-ART period to 22% in the late ART period (Ptrend <.001). Compared to HIV-1 and KSHV seronegatives, KSHV seropositives yielded an OR for KS of 26 (95%CI 11-62) in HIV-1 seronegative participants and an OR of 2501 (95%CI 1083-5776) in HIV-1 seropositive participants. HIV-1 increases the risk of KS in those infected with KSHV by 100-fold. Declines in KSHV seroprevalence coincide with ART rollout and with improvements in educational standards and general hygiene