A search for unknown blood-borne oncogenic viruses

In previous decades, infants who received blood transfusions shortly after birth or in utero might have been infected at a particularly vulnerable age by some blood-borne oncogen it virus. A cohort of such infants has therefore been followed into adult life to see if they suffered any excess of neoplastic disease or of non-neoplastic mortality. A total of 12,690 infants were identified who were transfused between 1 January 1942 and 31 December 1970, in most cases for the prevention or treatment of haemolytic disease of the newborn. All but 361 (2.8%) were found to have been registered with a National Health Service (NHS) practitioner and were followed in the NHS central records until they died, emigrated, were removed from NHS lists or until 1 January 1992, whichever occurred first. Mortality and cancer incidence were compared with that expected from national rates. No marked disparity was observed and there was no excess of childhood leukaemia. The incidence of non-Hodgkin's lymphoma at 15 to 49 years of age was about twice that expected, but the excess was not statistically significant.     

Morbidity and Mortality Associated with Typhoid Fever Among Hospitalized Patients in Hyderabad District,Pakistan, 2017-2018: Retrospective Record Review

BackgroundHyderabad, Pakistan, was the first city to witness an outbreak of extensively drug resistant (XDR) typhoid fever. The outbreak strain is resistant to ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, fluoroquinolones, and third-generation cephalosporin, thus greatly limiting treatment options. However, despite over 5000 documented cases, information on mortality and morbidity has been limited.ObjectiveTo address the existing knowledge gap, this study aimed to assess the morbidity and mortality associated with XDR and non-XDR Salmonella serovar Typhi infections in Pakistan.MethodsWe reviewed the medical records of culture-confirmed typhoid cases in 5 hospitals in Hyderabad from October 1, 2016, to September 30, 2018. We recorded data on age, gender, onset of fever, physical examination, serological and microbiological test results, treatment before and during hospitalization, duration of hospitalization, complications, and deaths.ResultsA total of 1452 culture-confirmed typhoid cases, including 947 (66%) XDR typhoid cases and 505 (34%) non-XDR typhoid cases, were identified. Overall, ≥1 complications were reported in 360 (38%) patients with XDR typhoid and 89 (18%) patients with non-XDR typhoid (P<.001). Ileal perforation was the most commonly reported complication in both patients with XDR typhoid (n=210, 23%) and patients with non-XDR typhoid (n=71, 14%) (P<.001). Overall, mortality was documented among 17 (1.8%) patients with XDR S Typhi infections and 3 (0.6%) patients with non-XDR S Typhi infections (P=.06).ConclusionsAs this first XDR typhoid outbreak continues to spread, the increased duration of illness before hospitalization and increased rate of complications have important implications for clinical care and medical costs and heighten the importance of prevention and control measures.     

Treatment of Aggressive Fibromatosis: the Experience of a Single Institution

AimsAggressive fibromatosis is a locally aggressive infiltrative low-grade tumour, although pathologically benign, and it does not metastasise, yet it can cause serious local distressing symptoms by virtue of local destruction and impairment of local function. The aim of this study was to emphasise the role of radiotherapy and adequate surgery in the treatment of fibromatosis in patients presenting with newly diagnosed or recurrent disease and to analyse our treatment results over 15 years for this rare tumour type.Materials and methodsFifty-four patients with confirmed diagnosis of aggressive fibromatosis treated at King Faisal Specialist Hospital between 1990 and 2006 were identified from our local cancer registry. Forty-seven patients had surgery: complete resection (R0) in 20 patients, incomplete surgery (R1/2) in 27 patients, and seven patients had biopsy only. Forty-five patients were treated with radiotherapy: 38 patients were treated with postoperative radiotherapy, three patients were treated with preoperative radiotherapy and four patients had radiotherapy as the only treatment. The radiotherapy dose ranged between 45 and 60 Gy (median 50.4 Gy). Three patients did not receive any form of treatment apart from biopsy, but were still included in the final analysis.ResultsFifty-two per cent (28/54 patients) of our patient population had tumour recurrence when first presented to King Faisal Specialist Hospital. The median age was 29.5 years (range 2–63 years). The most common site of involvement was the extremities (28 patients). Among the 54 patients (with primary and recurrent presentation) there were 10 local recurrences, all of which were within the original primary site. The 5-year progression-free survival and overall survival rates for the whole group were 75 and 95%, respectively. Univariate and multivariate Cox regression analysis showed that the depth of invasion significantly affected progression-free survival.ConclusionAggressive fibromatosis is effectively treated with surgery and postoperative radiotherapy. Patients first presenting with tumour recurrence may still have local tumour control comparable with newly diagnosed patients.     

Investigation of Bamboo Fibrous Tensile Strength Using Modified Weibull Distribution

Ethiopia has a large coverage of bamboo plants that are used for furniture making and house building. So far, researchers have not studied the strength of Ethiopian bamboo fibers, which are utilized for composite applications. The current study measured the strength of bamboo fibers based on various testing lengths and calculated the predictive tensile strength using a modified Weibull distribution. Moreover, the quality of the extraction machine is evaluated based on shape and sensitivity parameters. This research paper incorporates the coefficient of variation of the fiber diameters, considering the defects distribution through the length for measuring the predictive strength of the fibers. The fiber diameters were calculated using the area weight methods, which had its density measured using a Pycnometer. It has been examined that as the testing gauge length and coefficient variation of fiber diameter simultaneously increased, the tensile strength of the bamboo fibers decreased. The shape parameter, sensitivity parameter, and characteristic strength of Injibara bamboo (Y. alpina) are 6.02–7.83, 0.63, and 459–642 MPa, whereas Kombolcha bamboo (B. oldhamii) are 5.87–10.21, 0.33, and 408–638 MPa, as well as Mekaneselam bamboo (Y. alpina) are 5.86–9.63, 0.33 and 488–597 MPa, respectively.     

Next Wave of Targets in the Treatment of Advanced Renal Cell Carcinoma

While surgical resection has remained the mainstay of treatment in early-stage renal cell carcinoma (RCC), therapeutic options in the advanced setting have remarkably expanded over the last 20 years. Tyrosine kinase inhibitors targeting the vascular endothelial growth factor receptor (VEGF-TKIs) and anti-programmed cell death 1 (PD-1)/anti-programmed death-ligand 1 (PD-L1)-based immune checkpoint inhibitors (ICIs) have become globally accepted options in the upfront metastatic setting, with different ICI-based combination strategies improving overall survival compared to single-agent Sunitinib. Although some patients benefit from long-term responses, most eventually develop disease progression. Ongoing efforts to better understand the biology of RCC and the different mechanisms of acquired resistance have led to the identification of promising therapeutic targets. Belzutifan, a novel agent targeting the angiogenic pathway involving hypoxia-inducible factors (HIFs), has already been approved for the treatment of early-stage tumors associated with VHL disease and represents a very promising therapy in advanced RCC. Other putative targets include epigenetic regulation enzymes, as well as several metabolites such as adenosine, glutaminase and tryptophan, which are critical players in cancer cell metabolism and in the tumor microenvironment. Different methods of immune regulation are also being investigated, including CAR-T cell therapy and modulation of the gut microbiome, in addition to novel agents targeting the interleukin-2 (IL-2) pathway. This review aims to highlight the emergent novel therapies for RCC and their respective completed and ongoing clinical trials.     

Opposing roles of HDAC6 in liver regeneration and hepatocarcinogenesis

Histone deacetylase 6 (HDAC6), a deacetylase of p53, has emerged as a privileged inhibitory target for cancer therapy because of its deacetylating activity for p53 at K120 and K373/382. However, intricate roles of HDAC6 in hepatocellular carcinogenesis have been suggested by recent evidence, namely that HDAC6 ablation suppresses innate immunity, which plays critical roles in tumor immunosurveillance and antitumor immune responses. Therefore, it is valuable to determine whether HDAC6 ablation inhibits hepatocellular carcinogenesis using in vivo animal models. Here, we firstly showed that HDAC6 ablation increased K320 acetylation of p53, known as pro‐survival acetylation, in all tested animal models but did not always increase K120 and K373/382 acetylation of p53, known as pro‐apoptotic acetylation. HDAC6 ablation induced cellular senescence in primary MEFs and inhibited cell proliferation in HepG2 cells and liver regeneration after two‐thirds partial hepatectomy. However, the genetic ablation of HDAC6 did not inhibit hepatocarcinogenesis, but instead slightly enhanced it in two independent mouse models (DEN + HFD and DEN + TAA). Notably, HDAC6 ablation significantly promoted hepatocarcinogenesis in a multiple DEN treatment hepatocellular carcinoma (HCC) mouse model, mimicking chronic DNA damage in the liver, which correlated with hyperacetylation at K320 of p53 and a decrease in inflammatory cytokines and chemokines. Our data from three independent in vivo animal HCC models emphasize the importance of the complex roles of HDAC6 ablation in hepatocellular carcinogenesis, highlighting its immunosuppressive effects.     

Effects of Apnea,Obesity, and Statin Therapy on Proprotein Convertase Subtilisin/Kexin 9 Levels in Patients with Obstructive Sleep Apnea

ObjectivesObstructive sleep apnea (OSA) is a common condition closely related to obesity, insulin resistance, dyslipidemia, and cardiovascular disease. The aim of this study was to explore the possible relationship between OSA and proprotein convertase subtilisin/kexin type 9 (PCSK9).MethodsFull-night polysomnography was performed on 150 participants who were divided into three groups: controls, OSA patients on statin therapy, and OSA patients not on statin therapy. Biochemical markers, plasma low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses, and PCSK9 were determined.ResultsPCSK9 was highest in OSA patients on statins compared to the control group and to OSA patients not on statins (p = 0.036 and p = 0.039, respectively), after adjustment for body mass index (BMI). LDL diameter was greater in OSA patients not on statins compared to OSA patients on statins (p = 0.032). PCSK9 was highest in the group of patients with all three risk factors (diagnosed OSA, statins, BMI ≥25 kg/m²) compared to groups with no, one, and two risk factors (p = 0.031, p = 0.001, and p = 0.029, respectively). Presence of OSA, statin therapy, and BMI ≥25 kg/m² when combined were independently associated with higher levels of PCSK9 when adjusted for antihypertensive therapy, small dense LDL, and HDL 3c subclass (odds ratio = 2.849; interquartile range [1.026–7.912], p = 0.044).ConclusionStatin therapy was closely related to PCSK9. OSA along with obesity and statin use induces elevation of PCSK9.     

Jaw movements in patients with a history of pain: an exploratory study

The aims were to determine whether individuals with a past history of pain exhibit (i) altered jaw movement (e.g. reduced amplitude, increased jaw movement variability) in comparison with matched asymptomatic controls, and (ii) correlations between psychological measures (e.g. catastrophising) and altered jaw movement variables. Sixteen participants with a history of trigeminal neuropathic pain (TNP) and 15 age‐ and gender‐matched healthy controls had jaw movements recorded during open/close, free gum chewing and chewing at standardised rates. All completed the Pain Catastrophising Scale (PCS), the Pain Self‐Efficacy Questionnaire (PSEQ), and the Depression, Anxiety and Stress Scales (DASS). Velocity and amplitude for open/close and chewing, as well as variability, bias and mean square error for open/close jaw movements were compared between groups. Spearman's rank correlation coefficient was used to relate kinematic variables with psychological variables. Statistical significance: P < 0·05. There were no significant differences in mean jaw velocity and amplitude between the TNP and control groups during the open/close jaw movements or free or standardised chewing. In comparison with control, the TNP participants exhibited significantly greater variability, bias and/or mean square error during slow and/or fast opening, and significantly greater variance in velocity and/or amplitude during free and standardised chewing. There were significant negative correlations between PCS scores and velocity and/or amplitude of free and/or standardised chewing. This exploratory study suggests that individuals with a history of pain have altered patterns of jaw movements in comparison with asymptomatic control participants and that catastrophising may play a role in the manifestation of these altered jaw movements.