A bioinformatic analysis of the role of TP53 status on the infiltration of CD8+ T cells into the tumor microenvironment.

CD8+ T cells play basic roles in the immune system in a tumor microenvironment (TME) to fight cancer. Several reports have suggested signs of the involvement of tumor protein p53 (TP53) in a complex immune system network. Moreover, our previous research indicated that TP53 orchestrates the polarization and infiltration of macrophages into the TME. In the present study, the clinical function of TP53 status (wild/mutant) in CD8+ T cell infiltration was assessed using more than 10,000 The Cancer Genome Atlas (TCGA) samples from 30 cancer types through Tumor Immune Estimation (TIMER). Our investigation revealed that CD8+ T cell infiltration was higher in head and neck squamous cell carcinoma (HNSC) and uterine corpus endometrial carcinoma (UCEC) patients with wild-type TP53 than in those with mutant TP53. Wild-type TP53 conferred a good prognosis for HNSC and UCEC (P<0.05). In contrast, CD8+ T cell infiltration in lung adenocarcinoma (LUAD) patients with wild-type TP53 was much lower than in those with mutant TP53. Notably, clinical outcomes for LUAD with wild-type TP53 were poor (P<0.05). This study was the first to provide insights into the novel association of TP53 with CD8+ T cells infiltration in the TME in patients with HNSC, LUAD, and UCEC. Therefore, TP53 status acts as a prognostic marker, and this can be used as a basis to further study the effect of targeting TP53 in these patients. Furthermore, our study found that TP53 status was a reliable predictive factor and therapeutic target in patients with HNSC and UCEC.

A bioinformatic analysis of the role of TP53 status on the infiltration of CD8+ T cells into the tumor microenvironment

CD8+ T cells play basic roles in the immune system in a tumor microenvironment (TME) to fight cancer. Several reports have suggested signs of the involvement of tumor protein p53 (TP53) in a complex immune system network. Moreover, our previous research indicated that TP53 orchestrates the polarization and infiltration of macrophages into the TME. In the present study, the clinical function of TP53 status (wild/mutant) in CD8+ T cell infiltration was assessed using more than 10,000 The Cancer Genome Atlas (TCGA) samples from 30 cancer types through Tumor Immune Estimation (TIMER). Our investigation revealed that CD8+ T cell infiltration was higher in head and neck squamous cell carcinoma (HNSC) and uterine corpus endometrial carcinoma (UCEC) patients with wild-type TP53 than in those with mutant TP53. Wild-type TP53 conferred a good prognosis for HNSC and UCEC (P<0.05). In contrast, CD8+ T cell infiltration in lung adenocarcinoma (LUAD) patients with wild-type TP53 was much lower than in those with mutant TP53. Notably, clinical outcomes for LUAD with wild-type TP53 were poor (P<0.05). This study was the first to provide insights into the novel association of TP53 with CD8+ T cells infiltration in the TME in patients with HNSC, LUAD, and UCEC. Therefore, TP53 status acts as a prognostic marker, and this can be used as a basis to further study the effect of targeting TP53 in these patients. Furthermore, our study found that TP53 status was a reliable predictive factor and therapeutic target in patients with HNSC and UCEC.

Three cusps are better than two: bicuspid aortic valve and implications for military service.

Bicuspid aortic valve (BAV) is the most common congenital cardiac malformation. It is an aortopathy and is associated with other congenital heart disease. Although there is no mortality increase with BAV, the natural history increases the risk of aortic valve disease, aortic dilatation and infective endocarditis over the time frame of a full military career. Military service theoretically increases the risk of aortic dilatation and endocarditis in BAV. Conversely, there are some who have BAV who would not suffer any complications during their military career. Currently, potential UK Army recruits undergo personal/family history and physical examination plus an ECG and, although this goes beyond American Heart Association guidelines, it does not screen specifically for BAV. This would necessitate a transthoracic echo for each potential recruit but would be a considerable increase in resources-both time and financial. In addition to the recruitment medical, military personnel undergo frequent medicals, which could identify those who develop significant valvular disease. Those with mild valve disease are at lowest risk of complication. Those with aortic dilatation only remain a concern.

Evaluating cardioversion outcomes for atrial fibrillation on novel oral anticoagulants versus warfarin: experience at a tertiary referral centre.

BACKGROUND: Current guidelines recommend anticoagulation prior to cardioversion in patients with atrial fibrillation of >48 h or unknown duration to reduce thromboembolic risk. Therapeutic anticoagulation with warfarin, with INR between 2 and 3, is consistently achieved in approximately 60% of patients. AIMS: We evaluated outcomes and assessed differences in direct current cardioversion (DCCV) in patients treated with warfarin and novel oral anticoagulants (NOAC) at our institution. METHODS: A retrospective analysis of consecutive DCCV at a tertiary referral over 18 months was conducted. Analysis of cardioversion records allowed completion of a standardised dataset. Clinical variables recorded included (1) CHADSVASC score, (2) anticoagulant use, and (3) bleeding complications. RESULTS: During this period 187 DCCVs were scheduled; 119 on warfarin and 68 on NOAC. DCCV was deferred in 26% (n = 31) of the warfarin group and 4.4% (n = 3) of the NOAC group (p = 0.0002). The average time interval between referral and DCCV was 144.43 and 109.32 days for the warfarin and NOAC groups, respectively (p value = 0.023). 7.56% (n = 9) of the warfarin population had a bleeding event compared to a 2.94% total bleeding rate in NOAC group (p = 0.213). Deferral of elective DCCV and additional anticoagulant monitoring was estimated at €1160 per procedure. CONCLUSION: In elective cardioversions, the group anticoagulated with NOAC was less likely to have subtherapeutic anticoagulation and hence deferred procedures and had reduced health care consumption when compared to the group anticoagulated with warfarin.

Takotsubo cardiomyopathy after a dancing session: a case report.

INTRODUCTION: Stress-induced (Takotsubo) cardiomyopathy is a rare form of cardiomyopathy which presents in a manner similar to that of acute coronary syndrome. This sometimes leads to unnecessary thrombolysis therapy. The pathogenesis of this disease is still poorly understood. We believe that reporting all cases of Takotsubo cardiomyopathy will contribute to a better understanding of this disease. Here, we report a patient who, in the absence of any recent stressful events in her life, developed the disease after a session of dancing. CASE PRESENTATION: A 69-year-old Caucasian woman presented with features suggestive of acute coronary syndrome shortly after a session of dancing. Echocardiography and a coronary angiogram showed typical features of Takotsubo cardiomyopathy and our patient was treated accordingly. Eight weeks later, her condition resolved completely and the results of echocardiography were totally normal. CONCLUSIONS: Takotsubo cardiomyopathy, though transient, is a rare and serious condition. Although it is commonly precipitated by stressful life events, these are not necessarily present. Our patient was enjoying one of her hobbies (that is, dancing) when she developed the disease. This case has particular interest in medicine, especially for the specialties of cardiology and emergency medicine. We hope that it will add more information to the literature about this rare condition.

Comparison of higher-order aberrations after LASIK using disposable microkeratome 130 and 90 micron heads.

PURPOSE: To analyze and compare higher-order aberrations (HOAs) in cases of laser in situ keratomileusis (LASIK) flaps made using the Moria M2 disposable 130-micronm head with those made using the 90-micronm head. METHODS: Consecutive prospective comparative clinical trial. Ninety-four consecutive eyes of 48 patients were enrolled in this study. They were divided into two equal groups of 47 eyes that underwent wavefront-guided LASIK using VISX CustomVue (VISX, Santa Clara, CA) system. Corneal flap was created using the disposable Moria M2 130 micronm in the first group and the 90 micronm head in the second one. All patients were followed up for 6 months. Wavefront aberrations were measured at baseline, 1 month, and 6 months after surgery using the WaveScan (VISX Inc.) aberrometer. Root mean square (RMS) of HOAs, coma, and spherical aberration (SA) values were analyzed and compared in the two groups. RESULTS: At 6 months, values of RMS of HOAs, coma, and SA obtained from the 130-micronm head group were 0.32+/-0.10 micronm, 0.20+/-0.11 micronm, and 0.18+/-0.08 micronm, respectively. Values of RMS of HOAs, coma, and SA obtained from 90-micronm head group were 0.33+/-0.12 micronm, 0.19+/-0.10 micronm, and 0.15+/-0.08 micronm, respectively. Analyzing the data obtained revealed no statistically significant differences between the two groups. In each group, there was a significant decay of higher-order RMS and coma values from 1 month to 6 months. CONCLUSIONS: HOAs following use of Moria M2 disposable 90 micronm head are similar to those arising following use of the 130 micronm.

Results of combined phacoemulsification and viscocanalostomy in patients with cataract and pseudoexfoliative glaucoma.

PURPOSE: Coexisting pseudoexfoliation glaucoma (PEXG) and cataract represents a special challenge. Although phacotrabeculectomy is an effective procedure, it combines the risks of phacoemulsification and trabeculectomy. This study evaluates phacoviscocanalostomy to manage eyes with PEXG and cataract. METHODS: We conducted a prospective noncomparative study that included 30 consecutive eyes of 22 patients with uncontrolled PEXG and cataract. Phacoviscocanalostomy was performed in all. Success rate based on postoperative intraocular pressure (IOP) reduction and requirement for topical antiglaucoma medication was evaluated as the main outcome measure. Visual acuity and complication rates were secondary outcomes. RESULTS: The mean follow-up was 18.6 months +/-6.2 (SD) (range 12 to 36 months). There was statistically significant decrease in mean IOP from 25.3+/-5.2 mmHg preoperatively to 13.5+/-6.0 mmHg 1 day after surgery (p< .05), 12.3+/-3.1 mmHg at the final follow-up (p< .05), and at all evaluations to the last postoperative visit. Only three eyes (10%) required a single antiglaucoma medication to achieve the target IOP. A complete surgical success (IOP <21 mmHg without medication) was achieved in 90%, while a qualified success (IOP <21 mmHg with or without glaucoma medication) was achieved in 100% of cases. Complications included Descemet membrane microperforations (13.3%), macroperforation (3.3%), zonular dehiscence (6.6%), and transient postoperative IOP spike (3.3%). CONCLUSIONS: Phacoviscocanalostomy achieved excellent IOP control and visual acuity improvement in pseudoexfoliation patients with coexisting cataract and glaucoma. Complication rate was low and did not affect the surgical outcome.

Direct molecular analysis of the fragile X syndrome in a sample of Egyptian and German patients using non-radioactive PCR and Southern blot followed by chemiluminescent detection.

Molecular genetic analysis of individuals from 6 Egyptian and 33 German families with fragile X syndrome and 240 further patients with mental retardation was performed applying a completely non-radioactive system. The aim of our study was the development of a non-radioactive detection method and its implementation in molecular diagnosis of the fragile X syndrome. Furthermore, we wanted to assess differences in the mutation sizes between Egyptian and German patients and between Egyptian and German carriers of a premutation. Using non-radioactive polymerase chain reaction (PCR), agarose gel electrophoresis and blotting of the PCR products, followed by hybridisation with a digoxigenin-labelled oligonucleotide probe (CGG)5 and chemiluminescent detection, we identified the fragile X full mutation (amplification of a CGG repeat in the FMR-1 gene ranging from several hundred to several thousand repeat units) in all patients. We observed no differences in the length of the CGG repeat between the Egyptian and German patients and carriers, respectively. However, in one prenatal diagnosis, we detected only one normal sized allele in a female fetus using the PCR-agarose assay, whereas Southern blot analysis with the digoxigenin labelled probe StB 12.3 revealed presence of a full mutation. Our newly established nonradioactive genomic blotting method is based on the conventional radioactive Southern blot analysis. Labelling of the probe StB 12.3 with digoxigenin via PCR allowed the detection of normal, premutated and fully mutated alleles. For exact sizing of small premutated or large normal alleles, we separated digoxigenin labelled PCR products through denaturing polyacrylamide gelelectrophoresis (PAGE) and transfered them to a nylon membrane using a gel dryer. The blotted PCR-fragments can easily be detected with alkaline phosphate-labelled anti-digoxigenin antibody. The number of trinucleotide repeat units can be determined by scoring the detected bands against a digoxigenated M13 sequencing ladder. Our newly developed digoxigenin/chemiluminescence approach using PCR and Southern blot analysis provides reliable results for routine detection of full fragile X mutations and premutations.

Consanguineous matings in the Egyptian population.

A total of 26 554 Egyptians was ascertained to study the incidence of consanguineous marriages. They were of different ages, different socioeconomic standards, and from different areas. There were 7646 from urban areas, 11 280 from suburban areas, and 7628 from rural areas. The incidence of consanguineous matings in the general population was found to be 28.96% with an average inbreeding coefficient of 0.010, which could be considered high. The highest incidence was that in the rural areas. First cousin marriages occurred more often than the other types of consanguinity.

Unconventional protein sources: "date seeds".

Different varieties of Egyptian date seed were evaluated biochemically. The protein content of which was in the range of 7.13-10.36%, while the fat content was from 6.32-9.28%. Phosphorus, calcium and iron were determined in all experimental samples. One variety of date seed (Samany) were used for extensive determination of the amino acids constituents by acid hydrolysis, quantitative determination of some amino acids, and evaluation of their biological value on attempt to use the seeds as new protein sources. Weanling albino rats fed on a diet of protein level 5% lost weight, but no toxic signs were observed. Analysis of blood serum of rats, for total proteins, albumin globulin ratio and free nonessential/essential amino acid protein, showed the date seed protein to be of low biological value.

Unconventional protein sources: apricot seed kernels.

Hamawy apricot seed kernels (sweet), Amar apricot seed kernels (bitter) and treated Amar apricot kernels (bitterness removed) were evaluated biochemically. All kernels were found to be high in fat (42.2--50.91%), protein (23.74--25.70%) and fiber (15.08--18.02%). Phosphorus, calcium, and iron were determined in all experimental samples. The three different apricot seed kernels were used for extensive study including the qualitative determination of the amino acid constituents by acid hydrolysis, quantitative determination of some amino acids, and biological evaluation of the kernel proteins in order to use them as new protein sources. Weanling albino rats failed to grow on diets containing the Amar apricot seed kernels due to low food consumption because of its bitterness. There was no loss in weight in that case. The Protein Efficiency Ratio data and blood analysis results showed the Hamawy apricot seed kernels to be higher in biological value than treated apricot seed kernels. The Net Protein Ratio data which accounts for both weight, maintenance and growth showed the treated apricot seed kernels to be higher in biological value than both Hamawy and Amar kernels. The Net Protein Ratio for the last two kernels were nearly equal.

Evaluation of local varieties of Egyptian rice.

The different nutritional ingredients of the Egyptian varieties of rice (Giza 171, Giza 172, and Giza 180) were determined. 1. The nutritive values decreased in polished varieties more than in the hulled ones. 2. A wide variation in the protein content in the different varieties was recognized. 3. Giza 180 could be considered as the best Egyptian variety from the nutritional aspects.

Studies on some Egyptian foods. Part 1: Biochemical and biological evaluation.

General chemical analysis of some Egyptian legumes (lupinus termis and fenugreek seeds) and biological evaluation for their proteins were investigated. Results showed that lupinus termis and fenugreek seeds have high protein contents (with the exception of germinated fenugreek). They are good sources of calcium and phosphorus. Raw seeds gave low PER and NPR values. However, these values increase after roasting or germination.

Studies on some Egyptian foods. Part 2: The effect of protein on blood constituents of rats.

This study was undertaken to study the changes of the blood constituents of rats fed different proteins (lupinus termis, Guiza 1, 2 and balady; fenugreek seeds, raw, roasted, and germinated). The total serum protein for animals fed casein was slightly higher than those fed other proteins. Total serum protein of animals fed lupinus termis, roasted and germinated fenugreek was higher than those fed raw seeds. The albumin/globulin ratios showed a similar trend. The ratio of nonessential to essential free serum amino acids of rats fed non-protein diet was higher than those fed protein. Lupinus termis and fenugreek seeds are good sources of protein. Treatment of seeds either by heat of germination improves the nutritive value of the proteins.

Dorsal-column stimulation in the rehabilitation of patients with multiple sclerosis.

Two patients with chroic neurological deficit due to multiple sclerosis have been treated by percutaneous continuous dorsal-column stimulation. Motor, sensory, and bladder function improved significantly.