Human Xp/Yp telomere analysis by Southern-STELA

Telomeres are specialized structures designed to protect the ends of linear chromosomes. They are dynamic structures such that in normal somatic cells they constantly shorten as cell division progresses. There is compelling evidence that telomere shortening leads to cell senescence, a process perceived as the main cause of aging in higher mammals. Therefore, the features of telomere shortening are of great importance in understanding cell senescence and aging in general. By identifying unique subtelomeric regions, large enough to produce strong chemiluminescent signals, we have provided a new tool for Southern blot analysis of individual human Xp/Yp telomeres. We extend these results with quantitative fluorescence in situ hybridization using peptide nucleic acid probe (PNA Q-FISH) analysis of telomeres on the Y chromosome. Our results demonstrates unequal shortening dynamics between the p and q telomeres.     

Posttraumatic stress disorder symptoms and coping with the lockdown among help-seeking veterans before and during the COVID-19 pandemic

AimsTo compare the severity of posttraumatic stress disorder (PTSD) symptoms and of particular PTSD clusters among help-seeking veterans before and during the COVID-19 lockdown. The second aim was to identify the main coping strategies used.MethodsMale war veterans (N = 176) receiving outpatient treatment at the Referral Center for PTSD were assessed at baseline (12-18 months before the pandemic declaration in March 2020) and during the COVID-19 pandemic lockdown (March-June 2020). The Life Events Checklist for DSM-5, PTSD Checklist for DSM-5, and The Brief COPE were used.ResultsDirect exposure to the virus in our sample was low, and the majority of participants followed the preventive measures. The severity of the overall PTSD symptoms and of clusters of symptoms significantly decreased compared with the first assessment. At the second assessment, all participants still fulfilled the PTSD diagnosis criteria. During the lockdown, the participants used emotion-focused and problem-focused coping rather than dysfunctional coping.ConclusionThe severity of PTSD symptoms decreased during the lockdown. Further research is needed to study the trajectories of long-term psychopathology.

The COVID-19 pandemic has severely threatened the physical and mental health of individuals around the world. Stressors have included isolation, self-isolation or quarantine, restricted movement and physical contact, infection fears, loss of loved ones, lack of supplies, inadequate information (“infodemic”), financial loss, and social stigma (1-3). During emergencies, mental health requires special consideration due to increased rates of stress-related mental health problems and limited availability of mental health services (2-5).Depending on the emergency context, particular groups of people are at an increased risk of experiencing social and psychological problems (6), and ex-combatants have been repeatedly shown to be one of them (7).Exposure to a new traumatic or stressful life event might affect posttraumatic stress disorder (PTSD) symptoms. A growing body of research shows that such exposure is a risk factor for worsening of the condition in various groups of PTSD patients (8,9). This mainly happens if the subsequent event is of the same type as the initial stressors, serving as a reminder and as an additional traumatic factor with a “wear and tear” effect on the exposed person (10-13).Regarding the coping strategies used among PTSD patients, combat veterans with PTSD report a more ineffective and dysfunctional coping style, with the avoidance coping style as a predictive factor of the overall PTSD symptom severity (14-16). PTSD patients try to avoid confrontation with trauma-reminders, intrusive memories, and trauma-related thoughts and emotions (17,18). Some authors emphasize the importance of differentiating between coping strategies with PTSD symptoms and coping strategies with actual traumatic or stressful events as they depend on various factors related to the specific traumatic exposure (19).Twenty-five years after the Homeland War in Croatia (1991–1995), veterans still suffer from numerous health problems and have been highly prevalent among the users of the health facilities for PTSD treatment (20-22). The same is true for PTSD patients treated in the Referral Center of the Ministry of Health of the Republic of Croatia (RCPTSD) at the Clinical Hospital Center (CHC) Rijeka. A recent study revealed high rates of overall symptoms and severe posttraumatic symptoms (ie, complex PTSD) in this population years after the war ended (23).The COVID-19 pandemic lockdown in Croatia started on March 19, 2020. According to Oxford University, Croatia introduced the world''s strictest restrictions in relation to the number of the infected (24,25). On March 21, 2020, mental health experts from RCPTSD recommended self-help strategies for staying in good mental health and advice for front-liners on how to deliver psychological first aid (26,27). On the same day, the Croatian Psychiatric Association Expert Group released recommendations for the organization of psychiatric care, psychiatric interventions, and psychopharmacological treatment of mental conditions during the COVID-19 pandemic, and for de-escalation and appropriate communication techniques with aggressive patients (28-30). In RCPTSD, mental health service was restructured to be delivered via the internet or hotlines during the pandemic, with a possibility for urgent outpatient and inpatient treatment. On April 27, 2020, the lifting of restrictions began.To our knowledge, no study worldwide has examined the psycho-social correlates of the COVID-19 pandemic lockdown in veterans with PTSD. Therefore, we aimed to compare the severity of PTSD symptoms and of particular PTSD symptom clusters before and during the COVID-19 pandemic lockdown. Second, we identified the main coping strategies that veterans used during the lockdown.     

Impact of the novel CYP2C:TG haplotype and CYP2B6 variants on sertraline exposure in a large patient population

Sertraline is a commonly used SSRI antidepressant drug, metabolized by CYP2C19 and CYP2B6, that exhibits a substantial interindividual variation in clinical response, of which only a part can be attributed to known genetic variants. In the current study we have examined the role of a newly discovered ultrarapid CYP2C:TG haplotype and CYP2B6 variants in order to identify the possible missing heritability for such variation in sertraline response in a large patient population (n = 840). Compared to the reference group (CYP2C19*1/*1, n = 160), sertraline exposure was increased by 128% in CYP2C19 PMs (n = 29, p < 0.001) but decreased by about 20% in CYP2C19 ultrarapid metabolizers (Ums) (homozygous carriers of CYP2C19*17 and/or CYP2C:TG haplotype) with the diplotypes CYP2C19*17/*17, CYP2C:TG/TG, or CYP2C19*17/CYP2C:TG (n = 135, p < 0.003, p = 0.022, p < 0.003, respectively). Interestingly, in patients carrying the increased function CYP2B6*4 allele, and also carrying the CYP2C19*17 and CYP2C:TG alleles (n = 10), sertraline exposure was 35.4% lower compared to the reference group, whereas in subjects being poor metabolizers (PM) in both the CYP2C19 and CYP2B6 gene, the sertraline concentrations were raised by 189%. In summary, the CYP2C19 variants including the CYP2C:TG haplotype had a significant impact on sertraline metabolism, as well as the CYP2B6*4, *6, and *9 alleles. Knowing the CYP2B6 and CYP2C19 genotype, including the CYP2C:TG haplotype status, can prospectively be useful to clinicians in making more appropriate sertraline dosing decisions

Study highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Sertraline is a commonly used antidepressant subjected to metabolism by multiple enzymes with CYP2C19 playing a key role along with CYP2B6 and CYP3A4. Previous pharmacogenetic studies have reported significant effects of CYP2C19 and CYP2B6 genotypes on sertraline concentration, but with inconsistent findings probably reflecting that the concurrent effects of the genotypes have not been investigated in a large patient population. Furthermore, the studies have not accounted for the recently discovered CYP2C:TG haplotype associated with increased CYP2C19‐mediated metabolism.

• WHAT QUESTION DID THIS STUDY ADDRESS?

Our study investigated the impact of the novel CYP2C:TG haplotype on sertraline serum concentration in a large population genotyped for CYP2C19 (variants *2, *3, *4, and *17) and CYP2B6 (variants *4, *6, and *9).

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

This study demonstrates that the novel CYP2C haplotype (CYP2C:TG) is associated with increased rate of CYP2C19 metabolism of sertraline, as previously shown for escitalopram. In addition, patients carrying both the CYP2B6*4 variant and CYP2C19 genotypes encoding ultrarapid CYP2C19 metabolism are at increased risk of underexposure and therapeutic failure when treated with standard recommended doses of sertraline, whereas patients with only inactive or decreased function alleles of both CYP2C19 and CYP2B6 have a lower capacity for sertraline metabolism than CYP2C19 poor metabolizers carrying functional CYP2B6 alleles.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

Preemptive genotyping of sertraline patients would include CYP2C:TG, CYP2C19, and CYP2B6 variants to increase the dose precision of the drug in patients suffering from depression and/or anxiety.     

Pharmacotherapy and over-the-counter drug use among elderly in Belgrade,Serbia

From November 2012 to January 2013, 480 seniors were recruited at the Pubic Health Center in Belgrade, Serbia. The patients' records were validated by four independent investigators. Data on over-the-counter (OTC) drug use were collected through a questionnaire. Polypharmacy, an intake of ≥5 prescribed medications, reported in 10.4% of seniors, was associated with cardiovascular (odds ratio [OR] = 3.07; 95% confidence interval [CI] = 1.12–8.39) and endocrine diseases (OR = 2.25; 95% CI = 1.05–4.84) as well as with the number of treated chronic conditions (OR = 2.45; 95% CI = 1.75–3.44). The most frequently used OTC drugs were analgesics (metamizole, diclofenac and acetaminophen) and vitamins (vitamin C and vitamin B complex). The number of treated chronic conditions was associated with use of OTC drugs (OR = 1.17; 95% CI = 1.01–1.36). Multiple chronic conditions correlated with multiple OTC drug use (ρ = 0.125, p = 0.019). Our analysis indicated that the prevalence of polypharmacy and OTC drug use in the elderly are comparable to those in industrialized countries.     

Influence of the Hinge Axis Transfer Modality on the Three-Dimensional Condylar Shift Between the Centric Relation and the Maximum Intercuspation Positions

Purpose

The purpose of the study was to determine whether the hinge axis registration and the transfer modality (facebow transfer vs. average mounting) from the subject to the articulator affect the three-dimensional condylar shift between the centric relation (CR) and the maximum intercuspation (MI) position.

Material and Methods

The study was comprised of 32 fully dentate subjects (16 male and 16 female). Only the asymptomatic participants with normal occlusal relations (Angle class I) aged 20 - 33 (mean age 22.6 ± 4.7) met the inclusion criteria. Three-dimensional condylar shift (anteroposterior, superoinferior and mediolateral shift) between the centric relation position (CR) and the maximum intercuspation (MI) position was analyzed by means of Mandibular Position Indicator (SAM Prazisionstechnik GmbH, Muenchen, Germany).

Results

The average three-dimensional condylar shift was 0.13 ± 0.12 mm for facebow transfer and 0.22 ± 0.23 mm for average mounting. There were no statistically significant differences noted between genders. The results of the Mann-Whitney test showed statistically significant differences for anteroposterior and superoinferior condylar shift (P < 0.001). However, the difference in the mediolateral shift was not statistically significant.

Conclusions

In order to find discrepancies within the three-dimensional condylar shift, facebow transfer proved to be more accurate than the average mounting in the semi-adjustable articulator. However, the average value of three-dimensional shifts of the condyle did not differ from normal values and they did not have clinical significance. Thus, both ways of transfer modalities (facebow transfer and average mounting) in asymptomatic subjects with normal occlusion can be considered reliable.Key words: Hinge axis, facebow transfer, average mounting, centric relation, maximum intercuspation, mandibular position indicator     

Plasma Exchange in Elderly Patients

Plasma exchange (PE) is an extracorporeal blood purification technique designed for the removal of large molecular weight substances from plasma. Data regarding the use of PE in elderly patients is lacking, so this study analyzes the database of the Department of Dialysis at the University Hospital Center Zagreb (634 patients, 6237 procedures) for indications and complications in patients aged 65 years or older who were submitted to PE during the period from 1982 to 2007. A total of 50 patients in this age group were submitted to PE; their median age was 69 years (range 65–83). This population underwent 323 episodes of PE, mostly with albumin solution as the replacement fluid (94.0%), and blood access was usually via peripheral veins (72.0%). The most common indication for therapy (76.0%) was neurological (e.g. myasthenia gravis and Guillain–Barré syndrome), which was more common than in the entire population (i.e. of all age groups) (60%). The second most common indications were hematological diseases, followed by intoxications and Goodpasture's syndrome. Ninety-four percent of patients showed improvement, two patients with Guillain–Barré syndrome died, and a patient with pemphigus vulgaris had no change in clinical status, compared with 75% of younger patients whose status improved after PE. Complications occurred during 11.5% of treatments, compared to 3.9% in the younger group. The most common complications were clotting (3.7%), blood access difficulties (1.5%), mild-to-moderate allergic reactions (1.5%), and precordial oppression (0.6%). Plasma exchange is rarely used in the elderly population; however, when carried out by experienced staff, it is a safe and efficient method that may significantly improve the outcome of elderly patients with appropriate indications.     

Cerebral venous sinus thrombosis as a recurrent thrombotic event in a patient with heterozygous prothrombin G20210A genotype after discontinuation of oral anticoagulation therapy: How long should we treat these patients with warfarin?

Background

Cerebral venous sinus thrombosis is an uncommon condition with many clinical manifestations, and hereditary prothrombotic conditions such as factor Leiden V, deficiency of protein S, protein C and antithrombin III, as well as prothrombin gene mutation, may account for 10–15% of cases. To date, conflicting results have been reported for recurrent venous thrombosis in the patients with factor V Leiden and prothrombin G20210A mutation, since some studies have shown a higher risk for recurrent venous thrombosis in carriers of these two mutations than in non-carriers, and the last study showed higher risk only for carriers of double defect (homozygous or double heterozygous for this mutations).

Methods

Case report is presented.

Results

We report a case of cerebral sinus thrombosis as a recurrent thrombotic event in a patient with heterozygous prothrombin G20210A genotype after discontinuation of oral anticoagulation therapy.

Conclusion

Since many facts are controversial, the use of secondary prophylaxis for thrombosis in these patients is still a matter of debate without clear consensus recommendation. Data on the risk of recurrent thrombotic events in thrombophilic patient is insufficient. The main unclear question concerning these patients is: how long and whom should we treat with long-term anticoagulant therapy as secondary prophylaxis of DVT? The problem for practitioner is that we do not have guidelines and precise recommendations for secondary thromboprophylaxis in this or similar cases. This case is remarkable for its favorable and quick outcome and its rarity, because CSVT is an uncommon condition and heterozygous prothrombin G20210A genotype was only found predisposing factor for CSVT. Further studies of risk of recurrent venous thrombosis in patients with heterozygous prothrombin G20210A genotype with the larger sample size are required.

     

Informal care relationships and residential aged care recommendations: evidence from administrative data

Background

The Australian government recognises the importance of informal care to enable ageing in place. Yet, few multivariable studies have examined aspects of informal care that alter the probability of entry to residential care in Australia. Existing Australian and international studies show differing effects of informal care on entry to residential care.

Methods

We utilise unique administrative data on aged care assessments collected from 2010 to 2013, consisting of 280,000 persons aged 65 and over. Logistic regression models were fitted to measure the propensity to be recommended care in a residential care setting, disaggregated by characteristics of informal care provision.

Results

Providing some explanation for the divergent findings in the literature, we show that close familial carer relationships (partner or child) and coresidence are associated with recommendations to live in the community. Weaker non-coresidential friend or neighbour carer relationships are associated with recommendations to live in residential care for women, as are non-coresidential other relatives (not a child, partner or in-law) for both males and females. Non-coresident carers who are in-laws (for females) or parents have no impact on assessor recommendations. Despite these significant differences, health conditions and assistance needs play a strong role in assessor recommendations about entry to residential care.

Conclusion

Co-resident care clearly plays an important protective role in residential care admission. Government policy should consider the need for differential supports for co-resident carers as part of future aged care reform.

     

Collodion phenotype remains a challenge for neonatologists: A rare case of self‐healing collodion baby

We report a unique case of self‐healing collodion baby (CB) that was successfully managed despite the risk of potentially serious complications. Self‐healing CB is a rare and distinct outcome of collodion phenotype occurring in approximately 10% of the cases. The outcome depends on the initial assessment and adequate multidisciplinary approach.