Implementation and new insights in molecular diagnostics for HIV infection

Introduction: Acquired immunodeficiency syndrome (AIDS) is a kind of acquired disease that breaks down the immune system. Human immunodeficiency virus (HIV) is the causative agent of AIDS. By the end of 2016, there were 36.7 million people living with HIV worldwide. Early diagnosis can alert infected individuals to risk behaviors in order to control HIV transmission. Infected individuals are also benefited from proper treatment and management upon early diagnosis. Thanks to the public awareness of the disease, the annual increase of new HIV infections has been slowly declining over the past decades. The advent of molecular diagnostics has allowed early detection and better management of HIV infected patients.

Areas covered: In this review, the authors summarized and discussed the current and future technologies in molecular diagnosis as well as the biomarkers developed for HIV infection.

Expert Commentary: A simple and rapid detection of viral load is important for patients and doctors to monitor HIV progression and antiretroviral treatment efficiency. In the near future, it is expected that new technologies such as digital PCR and CRISPR-based technology will play more important role in HIV detection and patient management.     

Cholesterol-free diet and the physiologic hyperlipidemia of pregnancy in familial hypercholesterolemia

Longitudinal studies of the effects of a cholesterol-free diet and a less rigid 300 mg/day low cholesterol diet, both with a polyunsaturated to saturated fatty acid ratio of $\text{1.8}\text{1}$, were carried out preconception, during gestation, and postpartum in a woman heterozygous for familial hypercholesterolemia. On the cholesterol-free diet, during weeks 8–14 of gestation, plasma cholesterol was lowered 25% (from 310 to 230 mg/dl), and plasma low density lipoprotein cholesterol (C-LDL) (from 240 to 160 mg/dl), 33%. The 25% reduction in plasma cholesterol was slightly more than prviously reported decrements of 19% in 14 normal women during pregnancy, also receiving a cholesterol-free diet. The 300 mg cholesterol diet was not as hypocholesterolemic as the cholesterol-free diet. Its maintenance throughout gestation limited the within-pregnancy increments of total plasma cholesterol and C-LDL to 21% (352–426 mg/dl) and 14% (286–326 mg/dl) respectively. Both the cholesterol-free and the 300 mg cholesterol diet were well tolerated, and should be nutritionally adequate for pregnant women, since they contain more than the recommended amounts of high quality protein, vitamins, minerals, and calories for pregnant women. Cholesterol restricted diets during pregnancy in familial hypercholesterolemics should reduce the physiologic hypercholesterolemia of pregnancy, and potentially reduce the increased risk of coronary heart disease relative to the degree and duration of elevations of total and LDL cholesterol.     

Long‐term outcomes for different surgical strategies to treat left ventricular outflow tract obstruction in hypertrophic cardiomyopathy

Aims

Surgical intervention is used to treat dynamic left ventricular outflow tract obstruction (LVOTO) in hypertrophic cardiomyopathy. This study assesses the effect of different surgical strategies on long‐term mortality and morbidity.

Methods and results

In total, 347 patients underwent surgical intervention for LVOTO (1988–2015). Group A (n = 272) underwent septal myectomy; Group B (n = 33), septal myectomy and mitral valve (MV) repair; Group C (n = 22), myectomy and MV replacement; and Group D (n = 20), MV replacement alone. Median follow‐up was 5.2 years (interquartile range 1.9–7.9). The mean resting LVOT gradient improved post‐operatively from 71.9 ± 39.6 mmHg to 13.4 ± 18.5 mmHg (P < 0.05). Overall, 72.4% of patients improved by >1 New York Heart Association (NYHA) class; 58.9% of patients undergoing MV replacement alone did not improve their NYHA class. There were 5 perioperative deaths and 20 late deaths (>30 days). Survival rates at 1, 5 and 10 years respectively were 98.4, 96.9, 91.9% in Group A; 97.0, 92.4, 61.6% in Group B; 100.0, 100.0, 55.6% in Group C; and 94.7, 85.3, 85.3% in Group D (log‐rank, P < 0.05). Long‐term (>30 days) complications included atrial fibrillation (29.6%), transient ischaemic attack/stroke (2.4%) and heart failure hospitalisation (3.2%). There were 16 repeat surgical interventions at 3.0 years.

Conclusion

Septal myectomy is a safe procedure resulting in symptomatic improvement in the majority of patients. The annual incidence of non‐fatal disease‐related complications after surgical treatment of LVOTO is relatively high. Patients who underwent MV replacements had poorer outcomes with less symptomatic benefit in spite of a similar reduction in LVOT gradients.

     

Traumatic brain injury: review of current management strategies

Head injury is a common condition with a high morbidity and mortality. Serious intracranial haematomas require early recognition and evacuation to maximise chances of independent outcomes. Recent organisational changes have promoted the development of trauma units and major trauma centres where patients can go through triage and be managed in an appropriate environment, and the development of management pathways in intensive treatment units has resulted in improvements in the outcome of traumatic brain injuries. Evidence for the treatment of cerebral perfusion pressure, and management of hyperventilation, osmotherapy, tracheostomy, and leakage of cerebrospinal fluid (CSF) has accumulated during the last decade and is important in the management of patients in all clinical settings. Since head injury is commonly associated with maxillofacial injuries, this review will be relevant to all who deal with this aspect of trauma.     

Role of pro-IGF-II processing by proprotein convertase 4 in human placental development

Fetal growth restriction (intrauterine growth restriction, IUGR) is a leading cause of perinatal mortality. However, the causes of aberrant development of the placenta and, thus, of the fetus, are not currently known. Insulin-like growth factor II (IGF-II) has been shown to be an important regulator of fetoplacental growth. This growth factor must undergo posttranslational processing, and, thus, we hypothesized that aberrant processing of pro-IGF-II to IGF-II may be a cause of IUGR. Here, we have found that the proprotein convertase PC4 is expressed in the human placenta and that it cleaves pro-IGF-II to generate the intermediate processed form, IGF-II (1-102) and, subsequently, mature IGF-II (1-67), which are accounted for by the removal of terminal basic residues by carboxypeptidases. This processing confers the ability of IGF-II to activate invasive trophoblast cells through AKT phosphorylation, whereas inhibition of PC4 by a PC4-specific inhibitor blocks pro-IGF-II processing and reduces trophoblast cell migration, which can be partly restored by addition of mature IGF-II. Consistent with the hypothesis that IGF-II processing is implicated in IUGR, sera of patients carrying IUGR fetuses displayed elevated levels of pro-IGF-II. Thus, abnormal processing of IGF-II by PC4 may represent a previously uncharacterized mechanism involved in the pathophysiology of fetoplacental growth restriction, and elevated pro-IGF-II may be a useful clinical marker for risk of IUGR.     

Template-nucleated alanine-lysine helices are stabilized by position-dependent interactions between the lysine side chain and the helix barrel.

The helicity in water has been determined for several series of alanine-rich peptides that contain single lysine residues and that are N-terminally linked to a helix-inducing and reporting template termed Ac-Hel1. The helix-propagating constant for alanine (sAla value) that best fits the properties of these peptides lies in the range of 1.01-1.02, close to the value reported by Scheraga and coworkers [Wojcik, J., Altmann, K.-H. & Scheraga, H.A. (1990) Biopolymers 30, 121-134], but significantly lower than the value assigned by Baldwin and coworkers [Chakrabartty, A., Kortemme, T. & Baldwin, R.L. (1994) Protein Sci. 3,843-852]. From a study of conjugates Ac-Hel1-Ala(n)-Lys-Ala(m)-NH2 and analogs in which the methylene portion of the lysine side chain is truncated, we find that the unusual helical stability of Ala(n)Lys peptides is controlled primarily by interactions of the lysine side chain with the helix barrel, and only passively by the alanine matrix. Using 1H NMR spectroscopy, we observe nuclear Overhauser effect crosspeaks consistent with proton-proton contacts expected for these interactions.     

The relationship between mediastinal lymph node attenuation with parenchymal lung parameters in silicosis.

OBJECTIVE: Attenuation changes on computed tomography (CT) in mediastinal lymph nodes (LN) may be related to lung alterations and functional impairment in silicosis. DESIGN: CT and clinical data of 41 (64.2 +/- 8.3 years) males with silicosis were retrieved. Attenuation type (calcified, hyperdense, normodense) and calcification pattern (central, eccentric, dense, eggshell, speckled) of mediastinal LN were evaluated; LN attenuation of uncalcified LNs quantified on CT in six LN stations. Nodular profusion (CT-NP) and progressive massive fibrosis (CT-PMF) were graded. Relationships between LN, CT, lung function and clinical parameters were determined. RESULTS: LN sites were paratracheal (n = 39), subcarinal (n = 39), tracheobronchial (n = 37), aortopulmonary (n = 37), hilar (n = 27), and peri-oesophageal (n = 21). LNs were calcified, hyperdense and normodense in 107, 85 and 54 LN stations, respectively. Uniformly calcified LN was most common, followed by speckled calcification. Central, eccentric and eggshell calcification was rare. CT-NP scores > or = 16 were associated with higher LN attenuation and number of calcified LN stations than CT-NP scores < 16. PMF had no influence over LN morphology or calcification pattern. LN attenuation correlated with CT-PMF (r = 0.36, P = 0.01), CT-NP (r = 0.54, P < 0.001) and DLCO/VA (r = -0.33, P = 0.02). CONCLUSION: Uniformly calcified and hyperdense LNs are common in silicosis, and eggshell LN calcification is rare. There are associations between LN attenuation and lung function impairment, and CT grades of nodular profusion and PMF.