A Comparison of 3D Conformal and Deep Inspiratory Breath Holding vs. 4D-CT Intensity-Modulated Radiation Therapy for Patients with Left Breast Cancer.

BACKGROUND: Multimodality is required for the treatment of breast cancer. Surgery, radiation (RT), and systemic therapy were traditionally used. Pharmacotherapy includes different drug mechanisms, such as chemotherapy, hormone therapy, and targeted therapies, alone or in combination with radiotherapy. While radiation offers numerous benefits, it also has certain harmful risks. such as cardiac and pulmonary toxicity, lymphedema, and secondary cancer. Modern radiation techniques have been developed to reduce organs at risk (OAR) doses. MATERIALS AND METHODS: This study is a prospective feasibility trial conducted at the Fayium Oncology Center on patients with left breast cancer receiving adjuvant locoregional radiotherapy after either breast conservative surgery (BCS) or modified radical mastectomy (MRM). This study aimed to assess the proportion of patients who are fit both physically and intellectually to undergo breast radiotherapy using the deep inspiratory breath-holding (DIBH) technique, comparing different dosimetric outcomes between the 3D dimensional conformal with DIBH and 4D-CT IMRT plans of the same patient. RESULTS: D95 of the clinical target volume (CTV) of the target is significantly higher in the 3D DIBH plan than in the IMRT plan, with an average of 90.812% vs. 86.944%. The dosimetry of the mean heart dose (MHD) in the 4D-CT IMRT plan was significantly lower than in the 3D conformal with the DIBH plan (2.6224 vs. 4.056 Gy, p < 0.0064), and no significant difference between the two plans regarding mean left anterior descending artery (LAD) (14.696 vs. 13.492 Gy, p < 0.58), maximum LAD (39.9 vs. 43.5 Gy, p < 0.35), and V20 of the ipsilateral lung (18.66% vs. 16.306%, p < 0.88) was observed. Internal mammary chain (IMC) irradiation was better in the 4D-CT IMRT plan. CONCLUSIONS: Radiotherapy of the breast and chest wall with the 4D-CT IMRT technique appears not to be inferior to the 3D conformal with the DIBH technique and can be used as an alternative to the 3D conformal with the DIBH technique in patients meeting the exclusion criteria for performing the DIBH maneuver concerning coverage to target volumes or unacceptably high doses to OAR.

Discovery of Novel Isonipecotic Acid-Based Heteroaryl Amino Acid Derivatives as Potential Anticonvulsant Agents: Design, Synthesis, In-Silico ADME Study, and Molecular Docking Studies.

Background: Epilepsy is a neurological disorder characterized by anomalous brain activity, convulsions, and odd behavior. Several substituted-(naphthalen-2-yl)-3-(1H-indol-3-yl) allyl)-1,4-dihydropyridine-4-carboxylic acid derivatives (5a-j) were intended to be produced in the current research effort to reduce convulsions and seizures. Materials and Methods: The newly developed compounds were produced by the prescribed process. Numerous methods (infrared spectroscopy (IR), nuclear magnetic resonance (NMR), mass, elemental analysis, etc.) were used to characterize these substances. Several models were used to test each of these molecules for anticonvulsant activity. By using the rotarod and ethanol potentiation techniques, neurotoxicity was also evaluated. The study meticulously examined each parameter and showed absorption, distribution, metabolism, and excretion (ADME) predictions for each of the 10 congeners that were produced. In addition, studies on molecular docking employed the gamma amino butyric acid (GABA)-A target protein. Results: Anticonvulsant screening results identified compounds 5f, 5h, 5d, and 5b as the most efficacious of the series. All synthesized equivalents largely passed the neurotoxicity test. The results of molecular docking revealed significant interactions at the active site of GABA-A with LEU B: 99, TYR A: 62, Ala A: 174, and THR B: 202, and the outcomes were good and in agreement with in vivo findings. Conclusions: The study's findings showed that some substances had promising anticonvulsant properties that were comparable to those of the standard drug. The highly active novel anticonvulsant analogs may therefore represent a possible lead, and additional studies may result in a potential new drug candidate.

Menstrual symptoms variation among Lebanese women before and after the COVID-19 pandemic

Objectives: Pandemic diseases and the confinement measures due to COVID-19 infection have introduced acute and persistent psychosocial stressors for different individuals with a greater influence on females manifested through changes in the menstrual cycle. The objective of this study was to assess Lebanese female of reproductive age about their menstrual cycle, their mental health, and their lifestyle, throughout the COVID-19 pandemic, Beirut blast, and the economic crises. Methods: A cross-sectional online study conducted between October and December 2021, enrolled 398 Lebanese women using the snowball technique. The Menstrual Symptom Questionnaire (MSQ) was used to assess menstrual symptoms. A repeated measures ANOVA was used to assess factors associated with the variation in MSQ scores after vs before the pandemic. Results: Our results showed that a significantly higher number of days of menses, number of pads per day and total MSQ score were significantly found after the pandemic compared to before it. More distress (Beta=0.68), more post-traumatic stress disorder due to COVID-19 (Beta=0.19), a higher number of waterpipes smoked per week (Beta=1.20) and being infected by COVID-19 compared to not (Beta=3.98) were significantly associated with an increase in the MSQ score after the pandemic compared to before it. Conclusion: Our main findings indicate that females had irregular menstrual cycles, unpredictable bleeding pattern, and intense symptoms severity post COVID-19 pandemic. Furthermore, stress post COVID-19 and Beirut blast tended to be associated with increased menstrual symptoms. Thus, vulnerable women should be identified and offered appropriate care, information, and awareness regarding their menstrual period during a pandemic. (AU)

Puberty Induction in Adolescent Males: Current Practice.

Puberty is a developmental stage characterized by the appearance of secondary sexual characteristics which leads to complete physical, psychosocial, and sexual maturation. The current practice of hormonal therapy to induce puberty in adolescent males is based on published consensus and expert opinion. Evidence-based guidelines on optimal timing and regimen in puberty induction in males are lacking, and this reflects some discrepancies in practice among endocrinologists. It is worth mentioning that the availability of various hormonal products in markets, their different routes of administration, and patients/parents' preference also have an impact on clinical decisions. This review outlines the current clinical approach to delayed puberty in boys with an emphasis on puberty induction.

Menstrual symptoms variation among Lebanese women before and after the COVID-19 pandemic.

Objectives: Pandemic diseases and the confinement measures due to COVID-19 infection have introduced acute and persistent psychosocial stressors for different individuals with a greater influence on females manifested through changes in the menstrual cycle. The objective of this study was to assess Lebanese female of reproductive age about their menstrual cycle, their mental health, and their lifestyle, throughout the COVID-19 pandemic, Beirut blast, and the economic crises. Methods: A cross-sectional online study conducted between October and December 2021, enrolled 398 Lebanese women using the snowball technique. The Menstrual Symptom Questionnaire (MSQ) was used to assess menstrual symptoms. A repeated measures ANOVA was used to assess factors associated with the variation in MSQ scores after vs before the pandemic. Results: Our results showed that a significantly higher number of days of menses, number of pads per day and total MSQ score were significantly found after the pandemic compared to before it. More distress (Beta=0.68), more post-traumatic stress disorder due to COVID-19 (Beta=0.19), a higher number of waterpipes smoked per week (Beta=1.20) and being infected by COVID-19 compared to not (Beta=3.98) were significantly associated with an increase in the MSQ score after the pandemic compared to before it. Conclusion: Our main findings indicate that females had irregular menstrual cycles, unpredictable bleeding pattern, and intense symptoms severity post COVID-19 pandemic. Furthermore, stress post COVID-19 and Beirut blast tended to be associated with increased menstrual symptoms. Thus, vulnerable women should be identified and offered appropriate care, information, and awareness regarding their menstrual period during a pandemic.

Three Siblings With Woodhouse-Sakati Syndrome: A Case Report of A New Saudi Family.

Woodhouse-Sakati syndrome (WSS) is a rare autosomal recessive multi-system genetic disease caused by loss of function mutations in the DCAF17 gene on chromosome 2q31.1. The disease is characterized by gradual neurologic degeneration and polyendocrinopathy, particularly noteworthy for hypogonadism, beginning in early adolescence. Clinical features show wide variability with no clear genotype-phenotype correlation. The pathophysiology of WSS is unclear at present and no specific treatment is available other than hormone replacement which is administered in the course of individualized symptomatic multidisciplinary care. Genetic testing helps in confirming the diagnosis along with genetic counseling of the patient and family members. Here we report multiple cases of WSS in three siblings from a new Saudi Arabia family who were diagnosed with WSS as a consequence of a common founder mutation in the DCAF17 gene with DNA analysis showing a homozygous single nucleotide frameshift deletion (c.436delC) in exon 4 of the gene.

Constitutive overexpression of rice metallothionein-like gene OsMT-3a enhances growth and tolerance of Arabidopsis plants to a combination of various abiotic stresses.

Metallothioneins (MT) are primarily involved in metal chelation. Recent studies have shown that MT proteins are also involved in the responses of plants to various environmental stresses. The rice metallothionein-like gene OsMT-3a is upregulated by salinity and various abiotic stressors. A DNA construct containing the complete OsMT-3a coding sequence cloned downstream to the CaMV35S promoter was transformed into Arabidopsis and homozygous single-copy transgenic lines were produced. Compared to wild-type plants, transgenic plants showed substantially increased salinity tolerance (NaCl), drought tolerance (PEG), and heavy metal tolerance (CdCl2) as individual stresses, as well as different combinations of these stresses. Relevantly, under unstressed control conditions, vegetative growth of transgenic plants was also improved. The shoot Na+ concentration and hydrogen peroxide in transgenic plants were lower than those in wild-type plants. OsMT-3a-overexpressing Arabidopsis lines accumulated higher levels of Cd2+ in both shoots and roots following CdCl2 treatment. In the transgenic MT-3a lines, increased activity of two major antioxidant enzymes, catalase and ascorbate peroxidase, was observed. Thus, rice OsMT-3a is a valuable target gene for plant genetic improvement against multiple abiotic stresses.

Apigenin pretreatment enhances growth and salinity tolerance of rice seedlings.

Soil salinity is a limiting factor in rice production. Since flavonoids present in most plant tissues play multiple roles in plant-environment interactions, in this study, we focused on the contribution of flavone aglycone (Apigenin) to the adaptation of salinity-sensitive rice cultivar 'Koshihikari,' to salinity stress, for the first time. Rice seeds were soaked in Apigenin solution (10 ppm) for 24 h, then air-dried and grown hydroponically under 50 mM NaCl for 14 days. Apigenin pretreatment improved the growth of rice seedlings by enhancing shoot elongation and dry mass accumulation under both unstressed and NaCl-stress conditions, compared with that in the non-pretreated seedlings. Apigenin pretreatment significantly reduced Na+ accumulation in the salinity-stressed seedlings, and helped to maintain a lower Na+/K+ ratio in all plant organs, compared with that in the non-pretreated seedlings, possibly by regulating the expression of some important Na+ transporter-encoding genes (OsHKT2;1, OsCNGC1, OsSOS1). Higher levels of lipid peroxidation and hydrogen peroxide (H2O2) concentrations were observed in the shoots of the salinity-stressed seedlings; however, lower levels of lipid peroxidation and H2O2 concentration were detected in the Apigenin-treated seedlings. Apigenin pretreatment was associated with the induction of the rice antioxidant defense system represented by the induced activities of the antioxidant enzymes Catalase (CAT) and Ascorbate peroxidase (APX) in the roots, as well as by increased accumulation of the non-enzymatic antioxidants carotenoids and flavonoids in the shoots, relative to that in the untreated seedlings, under salinity stress conditions. Together, these results suggest that Apigenin pretreatment can alleviate the damaging effects of salinity on rice seedlings, presumably by regulating selective ion uptake by the roots and translocation to the shoots, thereby maintaining higher K+/Na+ ratios critical for normal plant growth under salinity stress, and by triggering the induction of the antioxidant defense system.

Differential responses of two Egyptian barley (Hordeum vulgare L.) cultivars to salt stress.

Although barley (Hordeum vulgare L.) is considered a salt tolerant crop species, productivity of barley is affected differently by ionic, osmotic, and oxidative stresses resulting from a salty rhizosphere. The current study was conducted to elucidate the mechanism of salt tolerance in two barley cultivars, Giza128 and Giza126. The two cultivars were exposed to 200 mM NaCl hydroponically for 12 days. Although both cultivars accumulated a large amount of Na+ in their leaves with similar concentrations, the growth of Giza128 was much better than that of Giza126, as measured by maintaining a higher dry weight, relative growth rate, leaf area, and plant height. To ascertain the underlying mechanisms of this differential tolerance, first, the relative expression patterns of the genes encoding Na+/H+ antiporters (NHX) and the associated proton pumps (V-PPase and V-ATPase) as well as the gene encoding the plasma membrane PM H+-ATPase were analyzed in leaf tissues. Salt stress induced higher HvNHX1 expression in Giza128 (3.3-fold) than in Giza126 (1.9-fold), whereas the expression of the other two genes, HvNHX2 and HvNHX3, showed no induction in either cultivar. The expression of HvHVP1 and HvHVA was higher in Giza128 (3.8- and 2.1-fold, respectively) than in Giza126 (1.6- and 1.1-fold, respectively). The expression of the PM H+-ATPase (ha1) gene was induced more in Giza128 (8.8-fold) than in Giza126 (1.8-fold). Second, the capacity for ROS detoxification was assessed using the oxidative stress biomarkers electrolyte leakage ratio (ELR) and the concentrations of malondialdehyde (MDA) and hydrogen peroxide (H2O2), and these parameters sharply increased in Giza126 leaves by 66.5%, 42.8% and 50.0%, respectively, compared with those in Giza128 leaves. The antioxidant enzyme (CAT, APX, sPOD, GR, and SOD) activities were significantly elevated by salt treatment in Giza128 leaves, whereas in Giza126, these activities were not significantly altered. Overall, the results indicate that the superior salt tolerance of Giza128 is primarily the result of the ability to counter Na+-induced oxidative stress by increasing antioxidant enzyme levels and possibly by increasing vacuolar Na+ sequestration and prevention of cellular K+ leakage.

Genetic polymorphisms of cytochrome P450-1A2 (CYP1A2) among Emiratis.

Cytochrome P450 1A2 (CYP1A2) is one of the CYP450 mixed-function oxidase system that is of clinical importance due to the large number of drug interactions associated with its induction and inhibition. In addition, significant inter-individual differences in the elimination of drugs metabolized by CYP1A2 enzyme have been observed which are largely due to the highly polymorphic nature of CYP1A2 gene. However, there are limited studies on CYP1A2 phenotypes and CYP1A2 genotypes among Emiratis and thus this study was carried out to fill this gap. Five hundred and seventy six non-smoker Emirati subjects were asked to consume a soft drink containing caffeine (a non-toxic and reliable probe for predicting CYP1A2 phenotype) and then provide a buccal swab along with a spot urine sample. Taq-Man Real Time PCR was used to determine the CYP1A2 genotype of each individual. Phenotyping was carried out by analyzing the caffeine metabolites using High Performance Liquid Chromatography (HPLC) analysis. We found that 1.4%, 16.3% and 82.3% of the Emirati subjects were slow, intermediate and rapid CYP1A2 metabolizers, respectively. In addition, we found that 1.4% of the subjects were homozygote for derived alleles while 16.1% were heterozygote and 82.5% were homozygote for the ancestral allele. The genotype frequency of the ancestral allele, CYP1A2*1A/*1A, is the highest in this population, followed by CYP1A2 *1A/*1C and CYP1A2 *1A/*1K genotypes, with frequencies of 0.825, 0.102 and 0.058, respectively. The degree of phenotype/genotype concordance was equal to 81.6%. The CYP1A2*1C/*1C and CYP1A2*3/*3 genotypes showed significantly the lowest enzyme phenotypic activity. The frequency of slow activity CYP1A2 enzyme alleles is very low among Emiratis which correlates with the presence of low frequencies of derived alleles in CYP1A2 gene.

Studies on N-Acetyltransferase (NAT2) Genotype Relationships in Emiratis: Confirmation of the Existence of Phenotype Variation among Slow Acetylators.

BACKGROUND AND PURPOSE: Individuals with slow N-acetylation phenotype often experience toxicity from drugs such as isoniazid, sulfonamides, procainamide, and hydralazine, whereas rapid acetylators may not respond to these medications. The highly polymorphic N-acetyltransferase 2 enzyme encoded by the NAT2 gene is one of the N-acetylators in humans with a clear impact on the metabolism of a significant number of important drugs. However, there are limited studies on N-acetylation phenotypes and NAT2 genotypes among Emiratis, and thus this study was carried out to fill this gap. METHODS: Five hundred seventy-six Emirati subjects were asked to consume a soft drink containing caffeine (a nontoxic and reliable probe for predicting the acetylation phenotype) and then provide a buccal swab along with a spot urine sample. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the genotype of each individual. Phenotyping was carried out by analyzing the caffeine metabolites using high-performance liquid chromatography (HPLC) analysis. RESULTS: We found that 78.5%, 19.1%, and 2.4% of the Emirati subjects were slow, intermediate, and rapid acetylators, respectively. In addition, we found that 77.4% of the subjects were homozygous or heterozygous for two nonreference alleles, whereas 18.4% and 4.2% were heterozygous or homozygous for the reference allele (NAT2*4), respectively. The most common genotypes found were NAT2*5B/*7B, NAT2*5B/*6A, NAT2*7B/*14B, and NAT2*4/*5B, with frequencies of 0.255, 0.135, 0.105, and 0.09, respectively. The degree of phenotype/genotype concordance was 96.2%. The NAT2*6A/*6A, NAT2*6A/*7B, NAT2*7B/*7B, and NAT2*5A/*5B genotypes were found to be associated with the lowest 5-acetylamino-6-formylamino-3-methyluracil/1-methylxanthine (AFMU/1X) ratios. CONCLUSIONS: There is a high percentage of slow acetylators among Emiratis, which correlates with the presence of nonreference alleles for the NAT2 gene. Individuals who carried NAT2*6A/*6A, NAT2*6A/*7B, NAT2*7B/*7B, or NAT2*5A/*5B genotypes might be at higher risk of toxicity with some drugs and some diseases compared to others, as these genotypes are associated with the slowest acetylation status.

Salinity-induced expression of HKT may be crucial for Na(+) exclusion in the leaf blade of huckleberry (Solanum scabrum Mill.), but not of eggplant (Solanum melongena L.).

Reduced Na(+) accumulation in the leaf blade is an important aspect of salinity tolerance and high affinity K(+) transporters (HKTs) are known to play a significant role in the process. Huckleberry and eggplant have previously been shown to display 'excluder' and 'includer' characteristics, respectively, under salt stress, but the underlying mechanisms have not been investigated. Here, we isolated the cDNA of the HKT homologs, Solanum scabrum HKT (SsHKT) from huckleberry and Solanum melongena HKT (SmHKT) from eggplant, and analyzed their expressions in different tissues under salt stress. SsHKT expression was markedly induced in the root (28-fold) and stem (7-fold), with a corresponding increase in Na(+) accumulation of 52% and 29%, respectively. Conversely, eggplant accumulated 60% total Na(+) in the leaf blade, with a lower SmHKT expression level in the root (3-fold). Huckleberry also maintained a higher K(+)/Na(+) ratio in the leaf blade compared to eggplant, due to the reduction of its Na(+) concentration and unaltered K(+) concentration. Functional analysis demonstrated that SsHKT-mediated Na(+) influx inhibited yeast growth under Na(+) stress, and that SsHKT did not complement the growth of the K(+) uptake-deficient CY162 strain under K(+)-limiting conditions. These results suggest that the Na(+) accumulation characteristics of both plants are caused by the differential expression of HKT genes, with SsHKT exerting a greater control over the ability of Na(+) to reach the leaf blade in huckleberry, than SmHKT does in eggplant.

Growth, physiological adaptation, and gene expression analysis of two Egyptian rice cultivars under salt stress.

Abiotic stressors, such as high salinity, greatly affect plant growth. In an attempt to explore the mechanisms underlying salinity tolerance, physiological parameters of two local Egyptian rice (Oryza sativa L.) cultivars, Sakha 102 and Egyptian Yasmine, were examined under 50 mM NaCl stress for 14 days. The results indicate that Egyptian Yasmine is relatively salt tolerant compared to Sakha 102, and this was evident in its higher dry mass production, lower leaf Na(+) levels, and enhanced water conservation under salt stress conditions. Moreover, Egyptian Yasmine exhibited lower Na(+)/K(+) ratios in all tissues examined under salinity stress. The ability to maintain such traits seemed to differ in the leaves and roots of Egyptian Yasmine, and the root K(+) content was much higher in Egyptian Yasmine than in Sakha 102. In order to understand the basis for these differences, we studied transcript levels of genes encoding Na(+) and K(+) transport proteins in different tissues. In response to salinity stress, Egyptian Yasmine showed induction of expression of some membrane transporter/channel genes that may contribute to Na(+) exclusion from the shoots (OsHKT1;5), limiting excess Na(+) entry into the roots (OsLti6b), K(+) uptake (OsAKT1), and reduced expression of a Na(+) transporter gene (OsHKT2;1). Therefore, the active regulation of genes related to Na(+) transport at the transcription level may be involved in salt tolerance mechanisms of Egyptian Yasmine, and these mechanisms offer the promise of improved salinity stress tolerance in local Egyptian rice genotypes.

Low grade uterine stromal sarcoma and squamous cell carcinoma associated with an IUD: a report of 2 cases.

BACKGROUND: Although intrauterine device (IUD) usage has not been linked to uterine cancer and has even been considered protective against neoplasia, sporadic cases of IUD-associated uterine malignancies have been reported. CASES: One cystic low grade stromal sarcoma of the uterus occurred in a 7-year IUD user, and 1 invasive endometrial squamous cell carcinoma following 25 years of IUD retention occurred in another. The latter case was notable for extensive in situ squamous cell carcinoma involving the entire uterine cavity and extending to the ectocervix and into both fallopian tubes. In situ hybridization for high-risk HPV DNA was negative. These findings raise the possibility of a non-HPV-related pathway for the squamous cell carcinoma case due possibly to prolonged chronic irritation and pyometra. CONCLUSION: The association of low grade stromal sarcoma with the IUD in the first case is extremely rare and most likely coincidental. The squamous carcinoma case, however, may have arisen via a non-HPV-related pathway, possibly related to IUD-induced chronic irritation and pyometra.