Hepatitis C prevalence and elimination planning in Pakistan,a bottom-up approach accounting for provincial variation

In Pakistan, substantial changes to hepatitis C virus (HCV) programming and treatment have occurred since the 2008 nationwide serosurvey estimated a 4.8% anti-HCV prevalence. In the absence of an updated national study, this analysis uses provincial data to estimate a national prevalence and the interventions needed to achieve elimination. Using a Delphi process, epidemiologic HCV data for the four provinces of Pakistan (accounting for 97% of the population) were reviewed with 21 subject-matter experts in Pakistan. Province-level estimates were inputted into a mathematical model to estimate the national HCV disease burden in the absence of intervention (Base), and if the World Health Organization (WHO) elimination targets are achieved by 2030 (80% reduction in new infections, 90% diagnosis coverage, 80% treatment coverage, and 65% reduction in mortality: WHO Elimination). An estimated 9,746,000 (7,573,000–10,006,000) Pakistanis were living with viraemic HCV as of January 1, 2021; a viraemic prevalence of 4.3% (3.3–4.4). WHO Elimination would require an annual average of 18.8 million screens, 1.1 million treatments, and 46,700 new infections prevented anually between 2022 and 2030. Elimination would reduce total infections by 7,045,000, save 152,000 lives and prevent 104,000 incident cases of hepatocellular carcinoma from 2015 to 2030. Blood surveys, programmatic data, and expert panel input uncovered more HCV infections and lower treatment numbers in the provinces than estimated using national extrapolations, demonstrating the benefits of a bottom-up approach. Screening and treatment must increase 20 times and 5 times, respectively, to curb the HCV epidemic in Pakistan and achieve elimination by 2030.     

Spindle cell lipoma breast

Spindle cell lipoma, which usually arises in the soft tissues, is rare in breast and is difficult to differentiate from primary mammary spindle cell tumor. Here, we present the case of a 48-year-old woman with a 3-cm, solitary, well-circumscribed and nontethered mass lying deep within the tissue of left breast, incidentally detected on routine mammography. The spindle cells proved to be immunoreactive to CD 34, but nonreactive to desmin and smooth muscle actin.     

Nano lipidic carriers for codelivery of sorafenib and ganoderic acid for enhanced synergistic antitumor efficacy against hepatocellular carcinoma

The current study focuses on the development and evaluation of nano lipidic carriers (NLCs) for codelivery of sorafenib (SRF) and ganoderic acid (GA) therapy in order to treat hepatocellular carcinoma (HCC). The dual drug-loaded NLCs were prepared by hot microemulsion technique, where SRF and GA as the drugs, Precirol ATO5, Capmul PG8 as the lipids, while Solutol HS15 and ethanol was used as surfactant and cosolvents. The optimized drug-loaded NLCs were extensively characterized through in vitro and in vivo studies. The optimized formulation had particle size 29.28 nm, entrapment efficiency 93.1%, and loading capacity 14.21%. In vitro drug release studies revealed>64% of the drug was released in the first 6 h. The enzymatic stability analysis revealed stable nature of NLCs in various gastric pH, while accelerated stability analysis at 25^◦C/60% RH indicated the insignificant effect of studied condition on particle size, entrapment efficiency, and loading capacity of NLCs. The cytotoxicity performed on HepG2 cells indicated higher cytotoxicity of SRF and GA-loaded NLCs as compared to the free drugs (p < 0.05). Furthermore, the optimized formulation suppressed the development of hepatic nodules in the Wistar rats and significantly reduced the levels of hepatic enzymes and nonhepatic elements against DEN intoxication. The SRF and GA-loaded NLCs also showed a significant effect in suppressing the tumor growth and inflammatory cytokines in the experimental study. Further, histopathology study of rats treated SRF and GA-loaded NLCs and DEN showed absence of necrosis, apoptosis, and disorganized hepatic parenchyma, etc. over other treated groups of rats. Overall, the dual drug-loaded NLCs outperformed over the plain drugs in terms of chemoprotection, implying superior therapeutic action and most significantly eliminating the hepatic toxicity induced by DEN in Wistar rat model.     

Translational researchers’ training and development needs,preferences, and barriers: A survey in a National Institute for Health Research Biomedical Research Centre in the United Kingdom

The objective was to identify translational researchers’ training and development needs, preferences, and barriers to attending training. This cross‐sectional study involved an online questionnaire survey. The research population comprised a convenience sample of translational researchers and support staff (N = 798) affiliated with the National Institute for Health Research Oxford Biomedical Research Centre. The response rate was 24%. Of 189 respondents, 114 were women (60%) and 75 were men (40%). The respondents were mainly research scientists (31%), medical doctors and dentists (17%), and research nurses and midwives (16%). Many of the respondents had attended at least one training course in the last year (68%). Training in statistics and data analysis was the most common training received (20%). Leadership training was the most wanted training (25%). Morning was the most preferred time of training (60%). Half a day was the ideal duration of a training course (41%). The main teaching hospital site was the most preferred location of training (46%). An interactive workshop was the most favored delivery style of training (52%). Most common barriers to attending training were the lack of time (31%), work (21%) and clinical commitments (19%), and family and childcare responsibilities (14%). Some differences in training needs, preferences, and barriers were found by gender and role, though these were not statistically significant. Translational researchers want short, easily accessible, and interactive training sessions during the working day. The training needs, preferences, and barriers to attending training need to be considered while developing inclusive training programs in biomedical research settings.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Training and continuing professional development of translational researchers is critical for research and innovation in healthcare, improving patient care, and career advancement.

• WHAT QUESTION DID THIS STUDY ADDRESS?

We studied the training and development needs and preferences of translational researchers and research support staff as well as barriers they encounter in attending training.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

In translational research settings, clinical researchers and research support staff prefer short and interactive training sessions in a convenient location during the working day, preferably in the morning for half a day. Translational researchers want training in leadership, research grant and fellowship writing, and statistics and data analysis. Lack of time and clinical commitments are the biggest barriers preventing clinicians and nurses from attending training.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

Translational research organizations should develop training programs that must consider training location, timing, and duration that suit clinicians, nurses, and other health professionals who work in very busy and highly demanding clinical settings. In addition, trainees’ gender, physical limitations, childcare and family commitments, and especially professional roles are also important factors to consider in developing inclusive training programs.     

Association of cholesteryl ester transfer protein genotypes with CETP mass and activity, lipid levels, and coronary risk

Alexander Thompson, MRes, MPhil; Emanuele Di Angelantonio, MD, MSc; Nadeem Sarwar, MRPharmS, MPhil; Sebhat Erqou, MD, MPhil; Danish Saleheen, MBBS, MPhil; Robin P. F. Dullaart, MD, PhD; Bernard Keavney, MD, FRCP; Zheng Ye, PhD; John Danesh, DPhil, FRCP

JAMA. 2008;299(23):2777-2788.

Context  The importance of the cholesteryl ester transfer protein (CETP) pathway in coronary disease is uncertain. Study of CETP genotypes can help better understand the relevance of this pathway to lipid metabolism and disease risk.

Objective  To assess associations of CETP genotypes with CETP phenotypes, lipid levels, and coronary risk.

Data Sources  Studies published between January 1970 and January 2008 were identified through computer-based and manual searches using MEDLINE, EMBASE, BIOSIS, Science Citation Index, and the Chinese National Knowledge Infrastructure Database. Previously unreported studies were sought through correspondence with investigators.

Study Selection  Relevant studies related principally to 3 common (TaqIB [rs708272], I405V [rs5882], and –629C>A [rs1800775]) and 3 uncommon (D442G [rs2303790], –631C>A [rs1800776], and R451Q [rs1800777]) CETP polymorphisms.

Data Extraction  Information on CETP genotypes, CETP phenotypes, lipid levels, coronary disease, and study characteristics was abstracted from publications, supplied by investigators, or both.

Results  Ninety-two studies had data on CETP phenotypes, lipid levels, or both in 113 833 healthy participants, and 46 studies had data on 27 196 coronary cases and 55 338 controls. For each A allele inherited, individuals with the TaqIB polymorphism had lower mean CETP mass (–9.7%; 95% confidence interval [CI], –11.7% to –7.8%), lower mean CETP activity (–8.6%; 95% CI, –13.0% to –4.1%), higher mean high-density lipoprotein cholesterol (HDL-C) concentrations (4.5%; 95% CI, 3.8%-5.2%), and higher mean apolipoprotein A-I concentrations (2.4%; 95% CI, 1.6%-3.2%). The pattern of findings was very similar with the I405V and –629C>A polymorphisms. The combined per-allele odds ratios (ORs) for coronary disease were 0.95 (95% CI, 0.92-0.99) for TaqIB, 0.94 (95% CI, 0.89-1.00) for I405V, and 0.95 (95% CI, 0.91-1.00) for –629C>A.

Conclusions  Three CETP genotypes that are associated with moderate inhibition of CETP activity (and, therefore, modestly higher HDL-C levels) show weakly inverse associations with coronary risk. The ORs for coronary disease were compatible with the expected reductions in risk for equivalent increases in HDL-C concentration in available prospective studies.

     

Production of high-quality and large lateral-size black phosphorus nanoparticles/nanosheets by liquid-phase exfoliation

The liquid phase exfoliation (LPE) of layered black phosphorus (BP) material is essential in the field of electronics. N-Methyl-2-pyrrolidone (NMP) is one of the most promising precursors for obtaining BP nanosheets/nanoparticles, but the longer sonication time leads to smaller production of phosphorene. Herein, for the first time, the large lateral size fabrication of phosphorene was attained through NMP solvent by optimizing the process parameters. The resultant dispersions were characterized by atomic force microscopy, X-ray powder diffraction, Raman spectroscopy, scanning electron microscopy, transmission electron microscopy, and ultraviolet-visible spectroscopy. The characterization results revealed that the average lateral sizes of BP nanoparticles were found to be 67.8 ± 18.6 nm and the lateral size of fabricated BP nanosheets was found to be 5.37 μm. Moreover, this research provides a strategic approach for the mass production of phosphorene for photodetection applications.

This work presented a cost-effective and simple route for the fabrication of high-quality and large lateral-size black phosphorus nanoparticles/nanosheets by liquid-phase exfoliation.