Stage Ie malignant lymphoma of paranasal sinus —A report of 5 cases and review of literature

Primary lymphoma is the most common nonepithelial malignant tumour arising from the paranasal sinus region. It occurs mostly in middle aged and elderly patients with a nonspecific clinical profile resembling that of commoner epithelial sinonasal malignancies. Modified Rappaport’s and the Working Formulation are the frequently used histopathological classification systems. Radiation therapy is the mainstay of treatment with excellent local control of the disease. Most of the failures occur at distant sites outside the treatment area or in the form of disseminateed disease. Chemotherapy, though used in limited number of patients in some series, seems to have a better role to play in the management of these tumours in future as most of the sinonasal lymphomas are of poorly differentiated variety or of unfavourable histology.     

Dynamics of endometrial thickness over time: a reappraisal to standardize ultrasonographic measurements in an infertility program

OBJECTIVE: To assess changes in endometrial thickness during different phases of spontaneous uterine contractions in the menstrual cycle. DESIGN: Prospective, longitudinal study. SETTING: Infertility clinic. PATIENT(S): Sixty-eight infertile patients seen for basic assessment between January 30 and July 1, 2002. MAIN OUTCOME MEASURE(S): Endometrial thickness on two-dimensional transvaginal ultrasonography. RESULT(S): Changes in endometrial thickness were seen on transvaginal ultrasonongraphy in 52 of 68 (76.47%) patients during spontaneous uterine contractions throughout the follicular phase of menstrual cycle. Changes involved the myometrium and subendometrium. Changes in thickness ranged from 1.3 mm to 2.8 mm, regardless of the day of study. CONCLUSION(S): Multiple measurements must be made to calculate a mean endometrial thickness that takes into account alterations due to contractions.     

Genital fistula--our experience

Genital fistulas cause immense physical and psychosocial problem in women's life. The present study was conducted to note the varieties of genital fistula as well as their causative factors and the results of the operative corrections. Altogether 42 patients with different varieties of genital fistula were enrolled in the study. The causative factors of the genital fistulas, specially, that of vesicovaginal fistulas were thoroughly enquired. After confirming the diagnosis, the operative corrections were undertaken. Among the varieties of genital fistula, 76.19% were vesicovaginal fistula, 11.90% were rectovaginal fistula and 4.76%, 4.76% and 2.38% cases of ureterovaginal, urethrovaginal and vesicocervical fistulas respectively. The primipara women were the major sufferers of genital fistulas due to obstetric grounds. Regarding aetiologies of vesicovaginal fistulas, 71.87% patients had obstetric reasons, after prolonged labour, instrumental delivery and after caesarean section due to obstructed labour. Abdominal hysterectomy (44.44%) topped the list of the gynaecological causes of vesicovaginal fistulas. The cases of ureterovaginal fistulas were after abdominal hysterectomy. One case of urethrovaginal fistula was due to some chemical application for correction of genital prolapses. The rectovaginal fistulas were mostly due to obstetric reasons. The success rate after the first attempt of repair of vesicovaginal fistula was 82.75% and overall failure was 10.34%. The other varieties of fistulas were repaired with 100% success rate. The incidence of genital fistulas can be reduced by vigilant obstetric care and meticulous surgery.     

Control of bacterial exoelectrogenesis by c-AMP-GMP

Major changes in bacterial physiology including biofilm and spore formation involve signaling by the cyclic dinucleotides c-di-GMP and c-di-AMP. Recently, another second messenger dinucleotide, c-AMP-GMP, was found to control chemotaxis and colonization by Vibrio cholerae. We have identified a superregulon of genes controlled by c-AMP-GMP in numerous Deltaproteobacteria, including Geobacter species that use extracellular insoluble metal oxides as terminal electron acceptors. This exoelectrogenic process has been studied for its possible utility in energy production and bioremediation. Many genes involved in adhesion, pilin formation, and others that are important for exoelectrogenesis are controlled by members of a variant riboswitch class that selectively bind c-AMP-GMP. These RNAs constitute, to our knowledge, the first known specific receptors for c-AMP-GMP and reveal that this molecule is used by many bacteria to control specialized physiological processes.Three major types of cyclic dinucleotide second messengers have been discovered in biological systems. The first to be found was c-di-GMP (Fig. 1A, Top), which serves as a regulator of diverse physiological changes in most bacterial lineages (1). The second, c-di-AMP (2), is an important signaling compound during bacterial sporulation and germination (3) and has also been found to regulate osmotic shock responses in Gram-positive bacteria (4, 5). More recently, a third type of cyclic dinucleotide called c-AMP-GMP (Fig. 1A, Bottom) was found to be required for Vibrio cholera virulence (6).Open in a separate windowFig. 1.Selective recognition of c-AMP-GMP by a natural aptamer. (A) Chemical structures of c-di-GMP and c-AMP-GMP. (B) Sequence and secondary structure of the 100 erfK RNA from G. metallireducens. P1, P2, and P3 identify base-paired substructures. M1 designates a mutant construct wherein position 20 is changed to G. Regions of constant, decreasing, and increasing RNA cleavage upon addition of ligand are indicated by yellow, red, and green circles, respectively. The arrowhead indicates the start of the RNA structure stability data derived from C. (C) PAGE analysis of in-line probing assays of 5′ ³²P-labeled 100 erfK in the presence (10 µM) of various cyclic dinucleotides. NR, T1, and ^‒OH designate lanes loaded with precursor RNA (Pre), RNA partially digested with RNase T1 (resulting in cleavage after G residues), and RNA partially digested with alkali (resulting in cleavage after every residue). Several RNase T1 cleavage product bands are labeled. Regions undergoing substantial change in spontaneous cleavage rates are labeled 1–4. The inosine-based analog of c-di-GMP is labeled c-di–IMP. (D) Plot of the fraction of riboswitch bound to ligand versus the log of the molar concentration (c) of the ligand. Data are derived from Fig. S2, and each point is the average of the normalized fraction of modulation at sites 1 and 2. Error bars indicate the SD of the average. Included are theoretical curves expected for one-to-one interaction between ligand and RNA for the K_D values given.Although bacterial c-AMP-GMP is formed via two 3′,5′-phosphodiester linkages, metazoans produce an analog with one 2′,5′-phosphodiester linkage and one 3′,5′-phosphodiester linkage (7–9). This natural structural variant has been identified as important for triggering innate immune responses in metazoans (7–11). Far greater diversity of cyclic dinucleotides is possible by varying either the nucleotide composition or the manner in which dinucleotides are joined. Therefore, many additional types of cyclic dinucleotides might await discovery in nature where they might regulate other critical cellular processes.Our approach to uncovering the chemical structures and biological functions of cyclic dinucleotide signaling compounds is to discover their RNA receptors. Three different riboswitch receptor classes have already been discovered that respond to c-di-GMP (12, 13) and c-di-AMP (5). Riboswitches are structured noncoding RNA (ncRNA) domains that selectively bind a small molecule or ion and thereby trigger a change in the expression of associated genes (14, 15). The majority of riboswitch ligands are composed of or derived from nucleotides, which supports the hypothesis that RNA-based metabolites and their riboswitch partners might descend from primordial RNA world organisms (16). If true, then cyclic dinucleotides and their receptors might be modern reflections of ancient signaling pathways. Regardless of their origins, the discovery of each new regulatory RNA motif that selectively recognizes a second messenger also reveals a superregulon for the signaling compound and the biology that it controls (5, 12, 13).Given that the diversity of natural cyclic dinucleotides might be greater than is currently known, and given that some riboswitch classes have undergone subtle changes to adapt to different ligands (17–20), we re-examined known cyclic dinucleotide riboswitch classes and their associated genes for evidence of unidentified ligands or riboswitch classes. Of special interest were those RNAs that both carry mutations in the core of the ligand-binding aptamer and have gene associations considered unusual for the parent riboswitch class. Through these efforts, we identified a subset of riboswitches within the c-di-GMP-I riboswitch class (12) that we hypothesized might bind a different ligand. In the current study, we demonstrate that these riboswitches recognize c-AMP-GMP and control a set of genes that are important for the utilization of iron(III) oxide in exoelectrogenesis.     

Resilience and Mental Health Among Syrian Refugee Children in Jordan

Refugee populations are at high risk of experiencing trauma and developing negative mental health outcomes. The resilience of Syrian refugee children is not well established as far as modifying the association between trauma and mental illness. A total of 339 Syrian refugee children aged 10 to 17 were surveyed to assess resilience, depression and history of trauma. All children reported exposure to at least one traumatic event, 48.6% reported exposure to highly salient traumatic events such as being held hostage, kidnapping or imprisonment. High rates of suicidal ideation and depression symptomatology were found. Resilience was strongly inversely related to depression. Relational support was found to be the most protective resilience factor and was the most highly correlated with less depressive symptomatology. Empowering children and families to build resilience through social support may be a viable prevention and management approach to other unaffordable or unavailable treatments for mental illnesses.

     

Dilated cardiomyopathy mutant tropomyosin mice develop cardiac dysfunction with significantly decreased fractional shortening and myofilament calcium sensitivity

Mutations in striated muscle alpha-tropomyosin (alpha-TM), an essential thin filament protein, cause both dilated cardiomyopathy (DCM) and familial hypertrophic cardiomyopathy. Two distinct point mutations within alpha-tropomyosin are associated with the development of DCM in humans: Glu40Lys and Glu54Lys. To investigate the functional consequences of alpha-TM mutations associated with DCM, we generated transgenic mice that express mutant alpha-TM (Glu54Lys) in the adult heart. Results showed that an increase in transgenic protein expression led to a reciprocal decrease in endogenous alpha-TM levels, with total myofilament TM protein levels remaining unaltered. Histological and morphological analyses revealed development of DCM with progression to heart failure and frequently death by 6 months. Echocardiographic analyses confirmed the dilated phenotype of the heart with a significant decrease in the left ventricular fractional shortening. Work-performing heart analyses showed significantly impaired systolic, and diastolic functions and the force measurements of cardiac myofibers revealed that the myofilaments had significantly decreased Ca(2+) sensitivity and tension generation. Real-time RT-PCR quantification demonstrated an increased expression of beta-myosin heavy chain, brain natriuretic peptide, and skeletal actin and a decreased expression of the Ca(2+) handling proteins sarcoplasmic reticulum Ca(2+)-ATPase and ryanodine receptor. Furthermore, our study also indicates that the alpha-TM54 mutation decreases tropomyosin flexibility, which may influence actin binding and myofilament Ca(2+) sensitivity. The pathological and physiological phenotypes exhibited by these mice are consistent with those seen in human DCM and heart failure. As such, this is the first mouse model in which a mutation in a sarcomeric thin filament protein, specifically TM, leads to DCM.     

Esophago-pleural fistula with pulmonary tuberculosis

A patient with clinical diagnosis of pulmonary tuberculosis and right sided hydropneumothorax found to have fistulous connection of pleura with oesophagus as evidenced by upper GI endoscopy and intrapleural instillation of radio-opaque dye. He was managed with intercostal chest tube drainage, antibiotics, antitubercular regimen and nasogastric tube feeding, resulting in eventless recovery subsequently.     

New RNA motifs suggest an expanded scope for riboswitches in bacterial genetic control

The expression of certain genes involved in fundamental metabolism is regulated by metabolite-binding "riboswitch" elements embedded within their corresponding mRNAs. We have identified at least six additional elements within the Bacillus subtilis genome that exhibit characteristics of riboswitch function (glmS, gcvT, ydaO/yuaA, ykkC/yxkD, ykoK, and yybP/ykoY). These motifs exhibit extensive sequence and secondary-structure conservation among many bacterial species and occur upstream of related genes. The element located upstream of the glmS gene in Gram-positive organisms functions as a metabolite-dependent ribozyme that responds to glucosamine-6-phosphate. Other motifs form complex folded structures when transcribed as RNA molecules and carry intrinsic terminator structures. These findings indicate that riboswitches serve as a major genetic regulatory mechanism for the control of metabolic genes in many microbial species.