Quantification of the T cell receptor excision circles (TRECs) has recently emerged as a useful non-invasive clinical and research tool to investigate thymic activity. It allows the identification of T cell production by the thymus. Quantification of TREC copies has recently been implemented as the preferred test to screen neonates with severe combined immunodeficiency (SCID) or significant lymphopenia. Neonatal genetic screening for SCID is highly important in countries with high rates of consanguinous marriages, such as Israel, and can be used for early diagnosis, enabling prompt therapeutic intervention that will save lives and improve the outcome of these patients. TREC measurement is also applicable in clinical settings where T cell immunity is involved, including any T cell immunodeficiencies, HIV infection, the aging process, autoimmune diseases, and immune reconstitution after bone marrow transplantation.
TAKE-HOME MESSAGES
• Severe combined immunodeficiency, a life-threatening condition, can be detected by neonatal screening.
• The earlier the detection and the quicker the implementation of appropriate treatment, the greater the likelihood for improved outcome, even cure, for the affected children.
• TRECs and KRECs quantification are useful screening tests for severe T and B cell immunodeficiency and can be used also to evaluate every medical condition involving T and B cell immunity.
Effects of early life psychosocial adversity have received a great deal of attention, such as maternal separation in experimental animal models and abuse/neglect in young humans. More recently, long-term effects of the physical stress of repetitive procedural pain have begun to be addressed in infants hospitalized in neonatal intensive care. Preterm infants are more sensitive to pain and stress, which cannot be distinguished in neonates. The focus of this review is clinical studies of long-term effects of repeated procedural pain-related stress in the neonatal intensive care unit (NICU) in relation to brain development, neurodevelopment, programming of stress systems, and later pain sensitivity in infants born very preterm (24–32 weeks’ gestational age). Neonatal pain exposure has been quantified as the number of invasive and/or skin-breaking procedures during hospitalization in the NICU. Emerging studies provide convincing clinical evidence for an adverse impact of neonatal pain/stress in infants at a time of physiological immaturity, rapidly developing brain microstructure and networks, as well as programming of the hypothalamic-pituitary-adrenal axis. Currently it appears that early pain/stress may influence the developing brain and thereby neurodevelopment and stress-sensitive behaviors, particularly in the most immature neonates. However, there is no evidence for greater prevalence of pain syndromes compared to children and adults born healthy at full term. In addressing associations between pain/stress and outcomes, careful consideration of confounding clinical factors related to prematurity is essential. The need for pain management for humanitarian care is widely advocated. Non-pharmacological interventions to help parents reduce their infant’s stress may be brain-protective.
Transoral laser microsurgery (TLM) was pioneered in the early 1970s as an approach to treat laryngeal pathology with precision and minimal thermal damage to the vocal cords. Over the last four decades, TLM has become an integral part of the treatment paradigm for patients with laryngeal cancer. TLM is one of the primary treatment options for early-stage laryngeal tumors. However, in recent years, surgeons have begun to develop TLM into a more versatile approach which can be used to address advanced laryngeal tumors. Although functional outcomes following TLM for advanced laryngeal disease are scarce, survival outcomes appear to be comparable with those reported for organ preservation strategies employing external beam radiation therapy (EBRT) and chemotherapy. In addition, TLM plays an important role in the setting of recurrent laryngeal cancer following primary irradiation. TLM has been demonstrated to decrease the need for salvage total laryngectomy resulting in improved functionality while retaining comparable oncologic outcomes. The aims of this review are to elucidate the indications, techniques, and oncological outcomes of TLM for advanced laryngeal cancers.
Despite a preoccupation in the medical literature with developing an effective approach for breaking bad news, the sources are based on personal opinion alone and only in some instances on qualitative research. Recognizing the gravity of this topic coupled with respect for the wisdom of the written and oral Jewish scriptures, this work is an attempt to delve into the diverse ancient writings to draw conclusions regarding a recommended methodology to guide and inform this task.
It is interesting to learn that most elements related to this topic have previously been raised in various forms in the scriptures. The issues range from where, when, and how the bearer of bad news should undertake this duty, to details such as the environment, the format, the speed, and depth of the details to be disclosed. The essence of this paper is to enrich the reader using both positive and negative examples found in the Jewish heritage. Adopting these principles will hopefully provide an effective method for performing this unpleasant obligation, with the goal of limiting harmful consequences as much as possible.
Pregnancy is a physiological hypercoagulable state, preparing the mother for the hemostatic challenge of delivery. However, this is associated with an increased risk of venous thrombosis and placenta-mediated complications, which present major challenges for mother and fetus. Although these conditions are heterogeneous in their pathophysiology, hereditary and acquired thrombophilia has been associated with recurrent pregnancy loss and gestational vascular complications, such as early-onset pre-eclampsia and placental abruption. Prevention of such placenta-mediated complications, which collectively complicate up to 15% of pregnancies, is a major issue for women’s health. Prospective interventional studies stratified by current knowledge of pathophysiological mechanisms related to placental and systemic hemostatic alterations will impact on the management of pregnancies at risk of these complications.
Heparanase is an endo-beta-D-glucuronidase that cleaves heparan sulfate (HS) side chains at a limited number of sites, activity that is strongly implicated with cell invasion associated with cancer metastasis, a consequence of structural modification that loosens the extracellular matrix barrier. Heparanase activity is also implicated in neovascularization, inflammation, and autoimmunity, involving migration of vascular endothelial cells and activated cells of the immune system. The cloning of a single human heparanase cDNA 10 years ago enabled researchers to critically approve the notion that HS cleavage by heparanase is required for structural remodeling of the extracellular matrix (ECM), thereby facilitating cell invasion. Heparanase is preferentially expressed in human tumors and its over-expression in tumor cells confers an invasive phenotype in experimental animals. The enzyme also releases angiogenic factors residing in the tumor microenvironment and thereby induces an angiogenic response in vivo. Heparanase up-regulation correlates with increased tumor vascularity and poor postoperative survival of cancer patients. These observations, the anticancerous effect of heparanase gene silencing and of heparanase-inhibiting molecules, as well as the unexpected identification of a single functional heparanase suggest that the enzyme is a promising target for anticancer drug development. Progress in the field expanded the scope of heparanase function and its significance in tumor progression and other pathologies such as inflammatory bowel disease and diabetic nephropathy. Notably, while heparanase inhibitors attenuated tumor progression and metastasis in several experimental systems, other studies revealed that heparanase also functions in an enzymatic activity-independent manner. Thus, point-mutated inactive heparanase was noted to promote phosphorylation of signaling molecules such as Akt and Src, facilitating gene transcription (i.e. VEGF) and phosphorylation of selected Src substrates (i.e. EGF receptor). The concept of enzymatic activity-independent function of heparanase gained substantial support by elucidation of the heparanase C-terminus domain as the molecular determinant behind its signaling capacity and the identification of a human heparanase splice variant (T5) devoid of enzymatic activity, yet endowed with protumorigenic characteristics. Resolving the heparanase crystal structure will accelerate rational design of effective inhibitory molecules and neutralizing antibodies, paving the way for advanced clinical trials in patients with cancer and other diseases involving heparanase.
High-altitude illnesses encompass the pulmonary and cerebral syndromes that occur in non-acclimatized individuals after rapid ascent to high altitude. The most common syndrome is acute mountain sickness (AMS) which usually begins within a few hours of ascent and typically consists of headache variably accompanied by loss of appetite, nausea, vomiting, disturbed sleep, fatigue, and dizziness. With millions of travelers journeying to high altitudes every year and sleeping above 2,500 m, acute mountain sickness is a wide-spread clinical condition. Risk factors include home elevation, maximum altitude, sleeping altitude, rate of ascent, latitude, age, gender, physical condition, intensity of exercise, pre-acclimatization, genetic make-up, and pre-existing diseases. At higher altitudes, sleep disturbances may become more profound, mental performance is impaired, and weight loss may occur. If ascent is rapid, acetazolamide can reduce the risk of developing AMS, although a number of high-altitude travelers taking acetazolamide will still develop symptoms. Ibuprofen can be effective for headache. Symptoms can be rapidly relieved by descent, and descent is mandatory, if at all possible, for the management of the potentially fatal syndromes of high-altitude pulmonary and cerebral edema. The purpose of this review is to combine a discussion of specific risk factors, prevention, and treatment options with a summary of the basic physiologic responses to the hypoxia of altitude to provide a context for managing high-altitude illnesses and advising the non-acclimatized high-altitude traveler.
In spite of the enormous progress of Western medicine during the past century there has not be a concomitant rise in the public’s satisfaction with the medical profession. Much of the discontent relates to problems in physician–patient communication. The multiple advantages of good communication have been clearly demonstrated by numerous careful studies. While the past few decades have witnessed much more attention given to teaching communication skills in medical schools, there are a number of factors that create new problems in physician–patient communication and counteract the positive teaching efforts. The “hidden curriculum”, the increased emphasis on technology, the greater time pressures, and the introduction of the computer in the interface between physician and patient present new challenges for the teaching of physician–patient communication.
This article focuses on contemporary Islamic attitudes towards the question of compensation to a non-relative live organ donor. This article presents the history of the debate on organ transplantation in Islam since the 1950s the key ethical questions. It continues by presenting the opinions of the main-stream ulema such as Tantawi and Qaradawi. The article ends with a conclusion that there must be no compensation made to a non-related live organ donor even a symbolic gift of honor (ikramiyya).
