Strategies in the management of post-burn breast deformities

Background

Burn injuries to the chest area may end up with severe breast deformity and asymmetry. They are frequently complex and unique to each case, affecting parenchymal development, breast implantation on chest wall, nipple areola complex position, infra-mammary fold definition, and skin envelope. Furthermore, contractures affecting adjacent territories may occur and add to the deformity. Surgical correction should address all the deformity components. Thus, a structured reconstructive plan that recruits different mammaplasty techniques and deals with adjacent territories is needed. This work presents different strategies used in treating severe post-burn breast deformities. Elaborate analyses of the deformities, surgical techniques, and outcomes are presented and a structured reconstructive plan is proposed.

Methods

Sixteen deformed breasts in 11 patients (mean age, 22 years) were managed. The techniques used included a variety of mastopexy techniques, prosthesis-based endoscopic breast reconstruction, and autologous breast augmentation with fat grafting or local flaps in some hypoplastic cases. Ancillary procedures to the neck, axilla, and abdomen were carried out to release the breast when tethered by their contractures.

Results

Considerable improvement and reasonable symmetry were achieved in most cases. All patients were satisfied with the results, tolerated the need for multiple procedures, and accepted residual minor asymmetries.

Conclusions

A post-burn breast deformity has a complex nature that may be addressed on multiple stages with different techniques of mastopexy, augmentation, and reconstruction. Ancillary procedures to a contracted adjacent territory may be needed to release the breast if tethered. Adopting a structured reconstructive plan may help obtain reproducible constant results. Level of Evidence: Level IV, therapeutic study.     

Relationship of regular physical activity with neuroelectric indices of interference processing in young adults

The relationship of physical activity with interference processing was examined using behavioral and neuroelectrical measures in young adults divided into more active and less active groups. The participants completed Stroop (i.e., color-naming) and reverse Stroop (i.e., word-meaning) tasks that differed in the level of difficulty while event-related potentials were assessed. In the low interference Stroop task, participants were asked to respond to the ink color of the word, while the meaning was either congruent or incongruent with the color. In the high interference reverse Stroop task, participants had to indicate the meaning of colored words while ignoring the color of the font. The results indicated that young adults in the more active group exhibited a shorter response time (RT) and a lower intra-individual variability of RT than did those in the less active group. These behavioral differences were associated with larger P2 and P3 and smaller N450 amplitudes in the Stroop task and with larger P2 and N2 and smaller N450 amplitudes in the reverse Stroop task. No differences were observed in the contingent negative variation (CNV) between the groups. These findings suggest that, for young adults, regular physical activity is positively associated with a better neural efficiency in resource allocation for tasks that require the ability to inhibit cognitive interference and provide evidence for the potential neural mechanisms underlying the improved Stroop performance.     

Reliability of long vs short COI markers in identification of forensically important flies

Aim

To compare the reliability of short and long cytochrome oxidase I gene fragment (COI) in identification of forensically important Diptera from Egypt and China.

Methods

We analyzed 50 specimens belonging to 18 species. The two investigated markers were amplified by polymerase chain reaction (PCR) followed by direct sequencing. Nucleotide sequence divergences were calculated using the Kimura two-parameter (K2P) distance model and neighbor-joining (NJ) phylogenetic trees.

Results

Although both tested fragments showed an overlap between intra and interspecific variations, long marker had greater completeness of monophyletic separation with high bootstrap support. Moreover, NJ tree based on the long fragment clustered species more in accordance with their taxonomic classification than that based on the short fragment.

Conclusion

In dipterous identification, it is recommended to use the long COI marker due to its greater reliability and safety.Necrophagous insects can serve as a valuable source of information for estimation of minimum post-mortem interval (PMI) in legal medicine. Most suitable for forensic purposes are species from the order Diptera (eg, Calliphoridae, Muscidae, and Sarcophagidae) (1-4). In PMI estimation, an important initial step is correct identification of these insects, which may be difficult by using the traditional morphology-based approach (5,6), because several forensically important fly species can hardly be distinguished morphologically (7-9). The limitations of morphological method can be overcome by gene sequences analysis, a fast and accurate method of species identification. Molecular analysis requires small tissue samples and is relatively insensitive to preservation conditions (1,10). Different mitochondrial (mt) and nuclear (nu) DNA markers are investigated as forensic tools. However, mtDNA is preferred because it can be easily extracted even from small or degraded samples (10). In addition, because of its strictly maternal inheritance and lack of genetic recombination, mtDNA haplotype is a good candidate for evolutionary and population genetics study.Mitochondrial cytochrome c oxidase subunit I (COI) sequences are a rapid and powerful tool for accurate identification of species across various taxa (7,11-14). Although COI has been extensively studied by forensic entomologists, resulting in a vast amount of DNA data, there is little agreement as to which portion of the gene needs to be sequenced. Although the 5′ end of COI is also the site of the proposed universal animal DNA “barcode” (11) and it has been successfully used in the identification of many blowfly species (12), this approach cannot identify some closely related species (12,15). Therefore, to optimize discrimination power between closely related species some authors suggested multi-gene approach (16,17). Surprisingly, a recent study using this approach revealed that phylogenetic tree based on COI fragment was similar to that based on 3 different gene fragments (16).Fragments of the COI sequence that show low sequence divergence within species but high divergences among species can be employed as taxon “barcodes,” and unknown samples can be accurately grouped to species with reference sequences of the “barcode library” (14,18,19). Therefore, it is paramount to evaluate not only discrimination power of these COI fragments between closely related species but also between species belonging to more than one family, because in a database an unknown sample will be compared to all reference samples. In the absence of an appropriate reference sample, unknown samples will simply group with the most closely matched reference sample (20). Thus, it is important to confirm that the investigated marker will not only be correctly assigned to a species but also that it will be in accordance with the traditional morphological classification. Therefore, we evaluated the discrimination power of the short (272-bp) COI fragment in the identification of the most forensically relevant flies (Calliphoridae, Sarcophagidae, and Muscidae) originating from Egypt and China in comparison to the long (1173-bp) COI fragment, and aimed to gather genetic data on common forensically important Diptera.     

Relationships between TIMP-1, CAIX,and clinical outcomes in Egyptian breast cancer

Serum levels of carbonic anhydrase IX (CAIX) and the tissue inhibitor of metalloproteinase 1 (TIMP-1) have been demonstrated to be associated with clinical outcomes. Elevated TIMP-1 levels have been associated with a poor prognosis of breast cancer. Therefore, this study was performed to explore the relationships between serum CAIX, TIMP-1, and clinical outcomes. One hundred and five female breast cancer patients, who do not receive adjuvant therapy at Mansoura University Hospital were recruited with informed consent for this study. Preoperative serum levels of CAIX and TIMP-1 were measured using an enzyme-linked immunosorbent assay. Among the breast cancer patients, 16.1 and 20.9 % had elevated TIMP-1 and CAIX l levels, respectively. In addition, 13.3 % had elevated both CAIX and TIMP-1 levels. Elevated serum levels CAIX was significantly associated with advanced histological grade, estrogen receptor status and progesterone receptor status. Moreover, Elevated TIMP-1 was significantly associated with number of tumor-positive lymph nodes and advanced histological grade. In Kaplan–Meier analysis, the disease-free survival (DFS) was lower in patients with high serum levels of CAIX and TIMP-1 compared to patients with normal serum concentration of CAIX and TIMP-1. Including TIMP-1, CAIX, and established prognostic factors in the multivariate analysis, the presence of elevated CAIX and TIMP-1 levels remained independent predictors of overall survival time (OS). A high serum TIMP-1 and CAIX levels were significantly associated with poorer DFS and OS among Egyptian primary breast cancer patients with elevated serum levels of CAIX and TIMP-1.     

MTHFR A1298C and C677T gene polymorphisms and susceptibility to chronic myeloid leukemia in Egypt

Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme regulating the intracellular folate metabolism which plays an important role in carcinogenesis through DNA methylation. We aimed to evaluate the association between MTHFR A1298C and C677T polymorphisms and the risks of chronic myeloid leukemia (CML). Eighty-five patients with CML and a control group containing 100 healthy, age and sex matched individuals were examined for MTHFR C677T and A1298C polymorphisms using polymerase chain reaction-restriction fragment-length (PCR-RFLP) method. The frequency of 677TT genotype in patients with CML was significantly higher compared to controls (OR = 2.513, 95% CI: 0.722-4.086, P = 0.025). No such association was shown for heterozygous 677CT (OR = 1.010, 95% CI: 0.460-2.218, P = 0.981). Moreover, for A1298C genotype, a statistically significant higher frequency of 1298CC was also detected in CML patients compared to control group (OR = 1.1816, 95% CI: 0.952-3.573, P = 0.036), 0.036). No such statistical significance was demonstrable for heterozygote 1298AC (OR = 1.046, 95% CI: 0.740-1.759, P = 0.092). In addition, patients with joint 677CT/1298AC or 677TT/1298CC genotypes showed an association with increased risk of CML (OR = 1.849, 95% CI: 0.935-2.540, P = 0.024; OR = 1.915, 95% CI: 1.202-3.845, P = 0.020 respectively). .A statistically significant increased risk of resistant to therapy was observed with 677CT and 1298AC genotypes (P = 0.001, P = 0.002 respectively). We conclude that both MTHFR 677TT and 1298CC polymorphisms have been associated with risk of CML and both 677CT and 1298AC genotypes are associated with higher risk of resistant to therapy.     

Real-world Treatment Patterns and Reasons for Therapy Selection in Patients with Advanced Hepatocellular Carcinoma in US Oncology Practices

BackgroundThe treatment landscape for advanced hepatocellular carcinoma (aHCC) is rapidly expanding beyond tyrosine kinase inhibitors (TKIs) in the first-line (1L) setting, with multiple TKIs and immune-checkpoint inhibitors (ICIs) now being evaluated in combination. Real-world evidence describing current treatment patterns and reasons for 1L and 2L treatment selection in aHCC is sparse.Patients and MethodsA retrospective cohort study with a cross-sectional survey element was conducted using Cardinal Health’s Oncology Provider Extended Network. U.S. medical oncologists identified adult aHCC patients initiating 1L systemic therapy between January 1, 2017 and July 31, 2019 and abstracted data from patient medical records. Data included provider characteristics, patient demographics and clinical characteristics, treatment regimens, and physician rationale for treatment regimen choice.ResultsA total of 44 medical oncologists provided data on 284 aHCC patients. The median age at 1L initiation was 61.5 years, and the majority were male (78%) and white (66%). Nearly half (47%) initiated 1L treatment in 2019, 34% were ECOG performance status 2+, and 63% were Child-Pugh Class B/C. Among the 284 aHCC patients, TKIs were used by 94% of patients in the 1L setting, comprised predominantly of sorafenib (54%) and lenvatinib (38%). ICIs were most common among the 90 patients (66%) who received 2L treatment.ConclusionIn the community-oncology practice setting, nearly all aHCC patients received sorafenib or lenvatinib in the 1L setting, while the majority of patients received an ICI in the 2L setting. With recent ICI approvals in aHCC, this marks the beginning of an increased use of ICIs in the 1L setting.     

Relationship between electroencephalography and magnetic resonance imaging findings after hypoxic-ischemic encephalopathy at term

Hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal morbidity and mortality. Electroencephalography (EEG) and brain magnetic resonance imaging (MRI) are frequently performed in these infants, but the prognostic value of the combined use of EEG and MRI needs additional exploration. The purpose of this study was to investigate, in neonates with HIE, the role of early EEG and conventional MRI in the prediction of infants at risk for persistent encephalopathy at 18 months of age. Thirty-four term infants with HIE were enrolled in this prospective study. EEG was recorded within the first 72 hours after birth and a brain MRI scan was done between 1 and 4 weeks of age. Denver Developmental Screening Test II was performed at 6, 12, and 18 months of age. Three infants (9%) had mild HIE, 21 infants (62%) had moderate HIE, and 10 infants (29%) had severe HIE. The EEG background was normal, moderately, severely, and extremely discontinuous in eight (24%), three (9%), sixteen (47%), and seven (20%) neonates, respectively. EEG background activities correlated significantly with HIE severity (p = 0.0001). MRI findings significantly correlated with EEG background (p = 0.001). Normal MRI scans and minimal basal ganglia lesions were always associated with normal EEG background. Patients with severe basal ganglia and thalamic lesions in MRI (n = 2) had extreme discontinuous EEG background. For the prediction of poor outcomes, abnormal EEG background activity had a sensitivity (Sn) = 100%, a specificity (Sp) = 100%, positive predictive value (PPV) = 100%, and negative predictive value (NPV) = 100%, whereas values of abnormal MRI scans were Sn of 100%, Sp = 43%, PPV = 82%, and NPV=100%. EEG background activity is the best element to predict abnormal outcomes. Severe basal ganglia and thalamic injuries on MRI scans are associated with poor outcomes. Otherwise, MRI does not contribute to the prediction of outcomes at 18 months of age.     

Role of peritoneal ultrasonography and ultrasound-guided fine needle aspiration cytology/biopsy of extravisceral masses in the diagnosis of ascites of undetermined origin

Background and study aimsAscites may be of undetermined origin despite comprehensive study. This study aimed to assess the accuracy and safety of conventional and interventional high-frequency peritoneal ultrasound in the diagnosis of patients with ascites of unclear origin.Patients and methodsA total of 62 patients were prospectively enrolled; they underwent conventional (3.5–5 MHz) and high-frequency (6–8 MHz) transabdominal peritoneal ultrasound to suggest the nature of ascites supplemented by fine needle aspiration cytology (FNAC) of ascites and/or core biopsy of the omentum or other extra-visceral masses for final histopathologic diagnosis. Laparoscopy or laparotomy was needed if biopsy was inconclusive.ResultsUltrasound-guided procedures were diagnostic in 55 (87.7%) patients. Thirty-six (58.1%) were benign, of whom 86% had tuberculous peritonitis, 26 (41.9%) were malignant, of whom 76.9% had peritoneal metastasis. High-frequency ultrasound was able to propose ultrasonographic criteria in a trial to diagnose the nature of ascites. Our proposed ultrasonographic criteria were based on the amount and texture of ascites in addition to the omental and mesenteric features. These were able to suggest the diagnosis with 80.7% sensitivity for malignant ascites and 75% specificity for benign ascites. Moreover, histopathological examination of tissues obtained by ultrasound-guided procedures increased the sensitivity to 88.5% and the specificity to 88.9% in diagnosing malignant and benign disease, respectively, with an overall diagnostic accuracy of 88.6%. These procedures were considered to be safe as only one major (haemoperitoneum) and two minor complications (temporary ascitic fistula) were reported.ConclusionHigh-frequency peritoneal ultrasound together with the minimally invasive ultrasound-guided FNAC/biopsy of extra-visceral lesions may be considered an effective and safe tool in the diagnosis of ascites of undetermined origin.     

In silico identification of potential SARS COV-2 2′-O-methyltransferase inhibitor: fragment-based screening approach and MM-PBSA calculations

In the present era, there are many efforts trying to face the emerging and successive waves of the COVID-19 pandemic. This has led to considering new and unusual targets for SARS CoV-2. 2′-O-Methyltransferase (nsp16) is a key and attractive target in the SARS CoV-2 life cycle since it is responsible for the viral RNA protection via a cap formation process. In this study, we propose a new potential inhibitor for SARS COV-2 2′-O-methyltransferase (nsp16). A fragment library was screened against the co-crystal structure of the SARS COV-2 2′-O-methyltransferase complexed with Sinefungin (nsp16 – PDB ID: 6WKQ), and consequently the best proposed fragments were linked via a de novo approach to build molecule AP-20. Molecule AP-20 displayed a superior docking score to Sinefungin and reproduced the key interactions in the binding site of 2′-O-methyltransferase. Three molecular dynamic simulations of the 2′-O-methyltransferase apo structure and its complexed forms with AP-20 and Sinefungin were performed for 150 nano-seconds to provide insights on the dynamic nature of such setups and to assess the stability of the proposed AP-20/enzyme complex. AP-20/enzyme complex demonstrated better stability for the ligand–enzyme complex compared to Sinefungin in a respective setup. Furthermore, MM-PBSA binding free energy calculations showed a better profile for AP-20/enzyme complex compared to Sinefungin/enzyme complex emphasizing the potential inhibitory effect of AP-20 on SARS COV-2 2′-O-methyltransferase. We endorse our designed molecule AP-20 to be further explored via experimental evaluations to confront the spread of the emerging COVID-19. Also, in silico ADME profiling has ascribed to AP-20 an excellent safety and metabolic stability profile.

The identification of AP-20 as a potential SARS COV-2 2′-O-methyltransferase inhibitor: fragment-based screening approach and MM-PBSA calculations.     

Study on a one-dimensional defective photonic crystal suitable for organic compound sensing applications

Organic-compound-based sensors have important applications, such as applications in geothermal power stations, the shoe industry, the extraction of vegetable oil, azeotropic calibration and medical science. Herein, a 1D photonic crystal (PC) with a defect has been used to develop a photonic-technology-based organic compound sensor with optimum performance. The structure of the proposed organic compound sensor consists of a water cavity sandwiched between two symmetric sub-PCs, which are composed of alternate layers of SiO₂ and ZnO. The proposed air/(SiO₂/ZnO)⁵/cavity/(SiO₂/ZnO)⁵/glass structure with the optimized structural parameters achieves a quality factor that varies between a minimum value of 4968.2 and a maximum value of 6418.5. The FOM and sensitivity values of the proposed sensing design are on the order of 10² and 10³, respectively. The LOD value of the proposed sensor is on the order of 10⁻⁵, which is very low, as is always expected for chemical sensing designs. Thus, the simple design and excellent performance make our design highly efficient and suitable for sensing applications in the industrial and biomedical fields.

Organic-compound-based sensors have important applications, such as applications in geothermal power stations, the shoe industry, the extraction of vegetable oil, azeotropic calibration and medical science.