Nevin Manimala

Ann Hum Biol. 2022 Jul 11:1-22. doi: 10.1080/03014460.2022.2100477. Online ahead of print.

ABSTRACT

BACKGROUND: CYP3A5 enzyme encoded by CYP3A5 is important for drug metabolism in gut and liver, whereas P-glycoprotein by ABCB1, is an ATP-dependent drug efflux pump which exports endo- and exogenous substances outside the cell. Aim: The study was to assess the prevalence of CYP3A5 alleles: *1, *2, *3, *4, *6 and *7, and C and T of ABCB1 in Poles, Belarusians and Bosnians and to compare it with the data reported from other European populations. Subjects and methods: Overall, 511 unrelated healthy subjects from Poland (n = 239), Belarus (n = 104) and Bosnia and Herzegovina (n = 168) were included in this study. Allele frequencies and statistical parameters (AMOVA version 2.9.3) were determined. Results: In Poles, Belarusians and Bosnians the *3 allele of CYP3A5 was the most common, and wild-type allele *1, were: 5.8%, 1.6% and 2.1%, respectively. Allele *2 was very rare, and alleles *4, *6 and *7 were not detected. For the populations mentioned above, the ABCB1 allele C was: 48.1%, 51.4%, 52.4%, respectively.

CONCLUSION: In compared populations, the distribution of CYP3A5 variants but not ABCB1, differed significantly. Alleles *4, *6 and *7 of CYP3A5 did not occur or occurred rarely.

PMID:35815612 | DOI:10.1080/03014460.2022.2100477

J Phys Chem B. 2022 Jul 10. doi: 10.1021/acs.jpcb.2c03676. Online ahead of print.

ABSTRACT

The abnormal aggregation of α-synulcein is associated with multiple neurodegenerative diseases such as Parkinson’s disease. The hydrophobic non-amyloid component (NAC) region of α-synuclein comprises the core of the fibril in vitro and in vivo. In this work, we study the aggregation landscape of the hydrophobic NAC region of α-synuclein using a transferrable coarse-grained force field, the associative memory water-mediated structure, and energy model (AWSEM). Using structural similarity, we can group metastable states on the free energy landscape of aggregation into three types of oligomers: disordered oligomers, prefibrillar oligomers with disordered tips, and ordered prefibrillar oligomers. The prefibrillar oligomers with disordered tips have more in-register parallel β strands than do the fully disordered oligomers but have fewer in-register parallel β strands than the ordered prefibrillar oligomers. Along with the ordered prefibrillar species, the disordered oligomeric states dominate at small oligomer sizes while the prefibrillar species with disordered tips thermodynamically dominate with the growth of oligomers. The topology of the aggregation landscape and observations in simulations suggest there is backtracking between ordered prefibrillar oligomers and other kinds of oligomers as the aggregation proceeds. The significant structural differences between the ordered prefibrillar oligomers and the disordered oligomers support the idea that the growth of these two kinds of oligomers involves kinetically independent parallel pathways. In contrast, the overall structural similarity between the fully ordered prefibrillar oligomers and the prefibrillar oligomers with disordered tips implies that two channels can interconvert on slower time scales. We also evaluate the effects of phosphorylation on the aggregation free energy landscape using statistical mechanical perturbation theory.

PMID:35815598 | DOI:10.1021/acs.jpcb.2c03676

Am J Perinatol. 2022 Jul 10. doi: 10.1055/s-0042-1750119. Online ahead of print.

ABSTRACT

INTRODUCTION: Respiratory conditions are the most common reason for admission of newborns to a neonatal care unit. The index of contractility (ICON) can be used to measure the thoracic fluid content (TFC) in neonates which is a significant parameter in cases presented with transient tachypnea of newborn (TTN).

OBJECTIVE: The objective was to compare TFC between newborn infants with TTN compared with other causes of respiratory distress (RD). We tested the hypothesis that TFC would be higher in infants with TTN.

STUDY DESIGN: In total, 105 newborns were enrolled at the delivery room and were categorized into three groups: TTN, other causes of RD, and control, according to physical examination and Chest X-Ray. TFC was measured within the first 6 hours for all infants and at 24 and 48 hours for the first two groups.

RESULTS: Demographic data showed higher male participants and use of antenatal steroid therapy in RD groups. TFC within the first 6 hours was higher in RD groups. However, TFC at 24 hours of ≤24 mL/kg, and TFC drop rate at 24 hours of >12% are statistically significant discriminators of TTN from non-TTN, with sensitivity and specificity of 97.1 and 47.1%, and 60 and 82.4%, respectively (Fig 1 and 2).

CONCLUSION: ICON can be used in conjunction with clinical parameters and CXR as a tool for differentiation between TTN and other causes of RD within the first 24 hours of life by using the cutoff value of TFC at 24 hours and TFC drop rate. This will allow earlier and optimum management of different causes of RD.

KEY POINTS: · Thoracic fluid content. · Neonatal respiratory distress. · Newborn.

PMID:35815571 | DOI:10.1055/s-0042-1750119

EMBO Rep. 2022 Jul 11:e55642. doi: 10.15252/embr.202255642. Online ahead of print.

NO ABSTRACT

PMID:35815565 | DOI:10.15252/embr.202255642

Tumori. 2022 Jul 10:3008916221111419. doi: 10.1177/03008916221111419. Online ahead of print.

ABSTRACT

BACKGROUND: Insertions of central venous catheters (CVC) has become a common practice in Onco-Hematologic Units to administer systemic treatments. Unfortunately they can cause complications influencing patient’s care-pathway significantly. Oncological patients have a higher thrombotic risk than the general population, therefore specific recent risk scores are spreading through the clinical practice, such as Khorana, Protecht, COMPASS-CAT, and Michigan scores.

METHODS: A retrospective cohort of 177 out of a total of 3046 outpatients accessing the Medical Day Hospital of Istituto Nazionale Tumori di Milano from March 2019 to February 2021 aged ⩾ 18 years who developed CVC complications was analyzed extracting clinical data from their medical records. Focusing on the risk factors, especially through recent risk scores to estimate the thrombotic risk we used Wilcoxon-test for continuous variables and the Pearson-Chi-Square test for categorical variables.

RESULTS: Anticoagulants resulted a protective factor mostly for partial CVC occlusion (p = 0.0001), preventing CVC occlusions. CVC occlusions were significantly associated with epitelial tumor histotype, (p = 0.0061). Complete CVC occlusions were significantly associated with peripherical inserted central venous catheters (PICC) (p < 0.0001). Catheter-related-thrombosis (CRT) was significantly associated with peripherical-inserted-central-venous-catheter, both when it was diagnosed clinically (p = 0.0121) and radiographically (p = 0.0168).There was a strong association between CRT and a high grade of Khorana Score (p = 0.0195), Protecht Score (p = 0.0412), COMPASS-CAT Score (p = 0.0027). A positive statistical trend was observed between the Michigan Score and CRT in patients carrying PICC (p = 0.053).

CONCLUSIONS: There are many different and various factors associated with higher or lower risk of CVC thrombotic complications, so it could be useful to test the recent risk scores to estimate thrombotic risk in oncological patients in clinical practice.

PMID:35815563 | DOI:10.1177/03008916221111419

Home Health Care Serv Q. 2022 Jul 9:1-20. doi: 10.1080/01621424.2022.2098083. Online ahead of print.

ABSTRACT

Caring for a person living with dementia (PLWD) can be challenging, making support services like respite important. Of the types of respite, research on paid professional in-home care specific to family caregivers of PLWD is limited. This study aimed to identify characteristics of dementia caregivers using paid in-home respite. A self-administered online survey (N = 98) examined use of in-home respite. Measures assessed depressive symptoms, burden, and self-rated health. Analyses included descriptive statistics and qualitative coding. Most respondents utilized weekly schedules of in-home respite with a moderate correlation between dependency and hours of respite. Caregivers’ self-reported average health, depressive symptoms, and mild-to-moderate burden. The majority of users had lowered perceived stress, were satisfied with services, and indicated the importance of in-home respite during a pandemic. Future research should assess changes in use of paid in-home respite services and overall landscape of respite options for dementia caregivers.

PMID:35815533 | DOI:10.1080/01621424.2022.2098083

Acta Chir Orthop Traumatol Cech. 2022;89(3):213-219.

ABSTRACT

PURPOSE OF THE STUDY Radial head fractures in paediatric patients account for 5-19% of all elbow injuries and approximately 1% of all fractures in children. Non-displaced fractures are treated with plaster cast fixation. If the fracture is displaced, we proceed to closed reduction, or to osteosynthesis in case of unstable fragments. If closed reduction fails, we opt for open reduction and osteosynthesis. The prospective randomised clinical study aims to compare the two methods of minimally invasive osteosynthesis using the pre-bent Kirschner wire or Prévot nail and to identify differences between them. MATERIAL AND METHODS The prospective randomised clinical study was conducted in 2015-2019. The final cohort included 32 patients who met the inclusion criteria. The patients in whom other osteosynthesis implants had been used or in whom open reduction had to be performed were excluded from the study. Also excluded were the patients with serious concomitant injuries of elbow. For patients included in the cohort, demographic data, precise evaluation of the displacement and location of the fracture as well as the duration of plaster cast fixation and osteosynthesis implants used were recorded. In the clinical part, the methods were compared based on the achievement of full range of motion in dependence on the degree of original displacement, use of osteosynthesis implant, and occurrence of early and delayed complications. Clinical and radiological outcomes were compared. In both types of minimally invasive osteosynthesis, Métaizeau surgical technique was used. RESULTS Based on the clinical trial criteria, 26 (81%) excellent, 4 (13%) good and 2 (6%) acceptable outcomes were achieved. In 3 cases the loss of rotation was up to 20°, in 1 case the loss of flexion was up to 10°. In one patient the loss of flexion was 15° and rotation up to 30°. In another patient the loss of rotation was up to 40°. The radiological assessment showed 14 (44%) excellent outcomes, 15 good (47%) and 3 (9%) acceptable outcomes. The statistical analysis of both the groups of the cohort using non-parametric tests revealed no statistically significant differences in individual demographic parameters. The comparisons of both types of osteosynthesis in dependence on the degree of displacement by non-parametric Fisher’s exact test showed no statistically significant difference in the radiologic or clinical results. The only statistically significant difference was observed in the duration of metal implant placement. DISCUSSION Comparable studies report excellent or good clinical outcomes in 80-95% of cases (1,13,16). In our cohort, excellent or good clinical outcomes were achieved in 30 patients (94%). In two patients, in whom Prévot nail was used, the outcomes were acceptable. Nonetheless, this fact did not result in any statistical significance when comparing the two methods separately or in comparisons based on the degree of displacement. CONCLUSIONS The comparison of the two methods of minimally invasive osteosynthesis revealed no statistically significant difference, namely not even when both the methods were compared based on the degree of displacement. When Kirschner wire is used, the possibility to remove the metal implant in the outpatient setting is considered to be an advantage. The drawback consists in potential penetration of the sharp Kirschner wire in the radiocapitellar joint, which we did not encounter when the second technique of osteosynthesis was used. The advantage of Prévot nail includes a lower risk of pin-tract infection. Key words: minimally invasive osteosynthesis, radial head, fracture, child.

PMID:35815489

Acta Chir Orthop Traumatol Cech. 2022;89(3):204-207.

ABSTRACT

PURPOSE OF THE STUDY Population aging is connected with an increased incidence of chronic diseases. A common related problem is chronic skin ulcers, which, while not life-threatening, can significantly decrease the quality of the patient’s life. The present study aims to evaluate new materials and methods to improve and accelerate the treatment of leg ulcers. MATERIAL AND METHODS Twenty-five patients with chronic ulcers treated using autologous growth factors applied on a nanofiber carrier were included in the cohort. The control group consisted of 15 patients treated using standard moist wound therapy. The surface area of the ulcer was measured on the 0th, 14th, 28th, 56th, 84th, 112th, 140th, 140th, and 168th day of treatment. Ulcer depth was measured on the 0th, 5th, 28th, 84th, and 168th day of treatment. Results were statistically processed and evaluated. RESULTS During the study, the defect area decreased in both the control and experimental group. Statistically significantly better results were observed in the experimental group relative to the progress of ulcer depth. The experimental group also had more healed ulcers. DISCUSSION Moistness is necessary for chronic wounds to heal; it is needed to ensure optimal cell growth, angiogenesis, and fibrinolysis. Wounds can be treated using non-active dressings with high absorption qualities; however, these do not guarantee optimal conditions for healing, or wounds can be treated with an interactive dressing that interacts with the wound surface. The third option for treatment is the use of bioactive materials that adhere to the wound and participate directly in the individual stages of healing. CONCLUSIONS The study found that autologous growth factors had statistically significant effects on the treatment of chronic ulcers. The authors believe that this method can accelerate the healing of primary post-injury or secondary postoperative wounds of lower leg soft tissues. Key words: trophic ulcer, autologous growth factors, microangiopathy, polyneuropathy, diabetes mellitus.

PMID:35815487

Acta Chir Orthop Traumatol Cech. 2022;89(3):199-203.

ABSTRACT

PURPOSE OF THE STUDY The hip fracture is the leading cause of disability and deaths in elderly. If left untreated, the hip fracture results in inability to walk, and therefore the patient is dependent on the other’s people help. The aim of this study was to determine the predictive values of the functional status, present comorbidities, and the types of treatment on the long-term functional status and mortality in patients with the hip fracture. MATERIAL AND METHODS We analyzed the data about the patients with the hip fractures treated in the period between 01.07.2006. and 01.07.2016., with the mean follow-up period between 34.3±4.9 months. The data included radiographs, age, comorbidities, functional status on admission, functional status on discharge, and follow-ups. RESULTS Female sex, increasing age, and poorer functional status upon admission, conservative treatment, trochanteric fracture, the presence of neurological or lung disease, diabetes, were all significant risk factors leading to poorer functional outcomes on the latest follow-up (p < 0.05). On the other hand, the patients who were mobile upon admission had a longer survival (38.1±3.51 months) as compared with the other patients (12.3±5.1 months; χ2=25.202, p = 0.001). Besides, the results of this study revealed that the direct, statistically significant relationship exists between the untreated internal and neurological diseases, and increased mortality and poorer functional outcomes on the latest follow-up. CONCLUSIONS These results are useful for the orthopedic and trauma surgeons, who are treating these patients, the physical medicine and rehabilitation specialists, who are performing the rehabilitation of these patients, but also the health policy makers, who may promote the programmes of healthy aging (treating the diseases, maintaining fitness, etc.) Key words: hip fracture; comorbidity; mortality; functional status.

PMID:35815486

Acta Chir Orthop Traumatol Cech. 2022;89(3):193-198.

ABSTRACT

PURPOSE OF THE STUDY Axial deformities of the lower limbs of various aetiologies are relatively common orthopaedic diagnoses in paediatric population. Fixed deformity is an indication for correction in order to reduce the pain and to delay the early osteoarthrosis of adjacent joints and pain. Temporary hemiepiphysiodesis is technically a fairly simple method for modulating growth at the level of the growth plate and thus correcting the skeletal axis. MATERIAL AND METHODS 59 patients who underwent axial deformity correction of lower limbs at KDCHOT FN Brno were retrospectively analysed. Group 1 consisted of 21 patients with Blount staples implantation, Group 2 consisted of 38 patients to whom eight-figure plates had been applied. Anthropometric parameters (BMI, age, gender, intermalleolar distance (IMD)), duration of therapy, X-ray parameters (anatomical lateral distal femoral angle (aLDFA), anatomical medial proximal tibial angle (aMPTA)) and complications were recorded. The rate of correction was evaluated as the difference in X-ray parameters before and after surgery with respect to the time interval of the therapy. RESULTS The groups were comparable in terms of anthropometric parameters (BMI (p=0.800), IMD (p=0.334), gender (p=0.87)). The only statistically significant difference was found when comparing the mean age of the groups (p=0.005), with Group 1 (12.7±0.7) containing patients with a higher mean age than Group 2 (11.6±1.5). The groups were also comparable in terms of the average rate of correction over a one-month interval (aLDFA p=0.393; aMPTA p=0.831). The mean correction rate for Group 1 was: aLDFA 0.52±0.20/month, aMPTA 0.12±0.08/month; for Group 2: aLDFA 0.56±0.28/month, aMPTA 0.12±0.20/month. Individual implants differed in the type of complications, but no significant statistical difference in the incidence of complications was found between the analysed groups (p=0.526). DISCUSSION Recently, the system of eight-figure plates has been adopted as a standard method for correction of axial deformities of limbs. Although the benefits of this system are indisputable, when comparing the average monthly correction rate, no significant difference was found between the system of eight-figure plates and Blount staples in our study. Another monitored parameter was the occurrence of complications, which was evaluated fairly strictly. Even in this case, no statistically significant difference was found. We believe that the issue of using eight-figure plates is still open, as evidenced by studies, which often produce different results and conclusions. Therefore, a precise evaluation of the indication for correction, including individual characteristics of patients, is needed. CONCLUSIONS Based on the results, it can be concluded that the use of eight-figure plates in comparison with Blount staples provides neither faster correction of axial deformities nor lesser occurrence of complications. It can therefore be argued that the Blount staples still have their place in the indication of correction of axial deformities. The use of eight-figure plates represents a suitable solution for children of younger age to whom anchoring of the screws of eight-figure plates is a suitable solution in the cartilaginous epiphysis of long bones of younger children. Key words: temporary hemiepiphysiodesis, growth plate, Blount staples, eight-figure plates.

PMID:35815485