The strong relationship between cardiovascular diseases (CVD), atherosclerosis, and endogenous or exogenous lipids has been recognized for decades, underestimating the contribution of other dietary components, such as amino acids, to the initiation of the underlying inflammatory disease. Recently, specific amino acids have been associated with incident cardiovascular disorders, suggesting their significant role in the pathogenesis of CVD. Special attention has been paid to the group of branched-chain amino acids (BCAA), leucine, isoleucine, and valine, since their plasma values are frequently found in high concentrations in individuals with CVD risk. Nevertheless, dietary BCAA, leucine in particular, have been associated with improved indicators of atherosclerosis. Therefore, their potential role in the process of atherogenesis and concomitant CVD development remains unclear. Macrophages play pivotal roles in the development of atherosclerosis. They can accumulate high amounts of circulating lipids, through a process known as macrophage foam cell formation, and initiate the atherogenesis process. We have recently screened for anti- or pro-atherogenic amino acids in the macrophage model system. Our study showed that glycine, cysteine, alanine, leucine, glutamate, and glutamine significantly affected macrophage atherogenicity mainly through modulation of the cellular triglyceride metabolism. The anti-atherogenic properties of glycine and leucine, and the pro-atherogenic effects of glutamine, were also confirmed in vivo. Further investigation is warranted to define the role of these amino acids in atherosclerosis and CVD, which may serve as a basis for the development of anti-atherogenic nutritional and therapeutic approaches.
BACKGROUND: The energy crisis hypothesis, which is a widely accepted model for the pathogenesis of myofascial pain, has been corroborated by experimental observations. However, the nature of the insult leading to the energy crisis remains elusive. A commonly cited model for this insult is the Cinderella hypothesis, suggesting that hierarchical recruitment of motor units leads to a disproportional load on small units, thus driving them towards an energy crisis. New findings cast doubt on this model, showing that in postural muscles motor units are recruited in rotation, rather than in a hierarchical order, precluding the formation of the so-called Cinderella units.
OBJECTIVE: To explore the influence of common myofascial predisposing factors such as muscle load and muscle strength on the relaxation time of postural muscle motor units, assuming they are recruited in rotation.
METHODS: A stochastic model of a postural skeletal muscle was developed which integrates the energy crisis model and motor unit rotation patterns observed in postural muscles. Postulating that adequate relaxation time is essential for the energetic replenishment of motor units, we explored the influence of different parameters on the relaxation time of individual motor units under varying conditions of muscle loads and muscle strengths.
RESULTS: The motor unit relaxation/contraction time ratio decreases with elevated muscle loads and with decreased total muscle strength.
Conclusions: In a model of a postural muscle, in which motor units are recruited in rotation, common predisposing factors of myofascial pain, such as increased muscle load and decreased muscle force, lead to shortened motor unit relaxation periods.
Therapy for inflammatory bowel diseases (IBD) has developed during recent years. Despite the availability of new therapeutic modalities, overall therapy success remains modest, and complete remission is usually achieved and maintained in approximately 30% of patients only. This observation can be explained by a number of reasons. First, the involvement of multiple genetic loci combined with differential environmental exposures suggests that IBD represent a continuum of disorders rather than distinct homogeneous disease entities. This diversity is translated into different disease course patterns, wherein some patients experience quiescent disease whereas others suffer from a relentless disease course. Hence, basic disease pathogenesis sets the stage for differential treatment responses. To date, IBD therapy is based on immunosuppression which does not take basic disease variability into account. Treatments are prescribed based on statistical considerations related to the response of the average patient in clinical trials rather than on personal considerations. Treatment outcomes can potentially be improved if physiologic considerations are inte¬grated into the drug selection process. In one approach, drugs can be targeted at known patient dysfunc¬tional processes such as in the case of patients carrying autophagy-related genetic polymorphisms being treated with rapamycin, a drug that inhibits mTOR inhibitor and enhances autophagy. Another alternative would be to use a systems approach to perform unsupervised, high-throughput screening in order to derive predictive treatment biomarkers and mechanistic insights associated with response to specific drug therapy. Additional predictive markers for drug safety are needed as well. Caveats and directions for needed future studies are outlined.
Background: Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy in India. The aggressiveness of OSCC is analyzed not only based on the dysplastic features and tumor infiltration pattern, but also by means of the stromal changes that pave the way for an invasion into the connective tissue. The role of elastic fibers in the progression of OSCC is still unknown because of sparse literature and the masking effect of overlying inflammatory cells and the lower number of elastic fibers in the lamina propria. The present study provides further insight into the qualitative assessment of elastic fibers in various grades of dysplasia and OSCC.
Objectives: To analyze the morphological changes exhibited by the elastic fibers in epithelial dysplasia and OSCC.
Materials and methods: Two sections were cut from each of 60 samples of varying grades of OSCC and 60 samples of varying grades of epithelial dysplasia followed by staining with hematoxylin and eosin and Verhoeff–Van Gieson stain.
Results: Statistically significant results were obtained for qualitative analysis of elastic fibers. A change in density and orientation to overlying epithelium and tumor islands was seen on progressing from well-differentiated to poorly differentiated OSCC and in progressing grades of dysplasia.
Conclusion: The uniqueness of this study lies in the exploration of elastic fibers in dysplasia and well-differentiated OSCC, a less explored field. The study of the connective tissue stromal changes can be used as an adjunct to histological grading.
Objective: To review current medical literature on the risks and potential benefits of e-cigarette use and its permissibility under Jewish law.
Methods: A survey of current medical literature about the risks and potential benefits of e-cigarette use, and a review of existing rabbinic literature regarding both combustible and e-cigarette products.
Results: E-cigarettes contain fewer harmful materials than do combustible cigarettes. However, they are not risk-free. Their skyrocketing use among youth is of concern, as e-cigarettes lead to nicotine addiction and are a gateway to combustible cigarettes. Preliminary data indicate that e-cigarettes increase the risk of myocardial infarction, chronic obstructive pulmonary disease (COPD), and emphysema and are no more effective as aids to smoking cessation than US Food and Drug Administration (FDA)-approved interventions with acceptable safety profiles. Few halakhic decisors have opined on the permissibility of e-cigarettes, but extrapolating from halakhic discussions regarding combustible cigarettes strongly suggests that they would prohibit e-cigarettes based on government warnings and preliminary data demonstrating increased risk of cardiovascular and respiratory diseases, at the least because of possible danger (safek sakana). Among youth and pregnant women, for whom e-cigarettes are particularly dangerous and for whom the government has administered explicit warnings, a Jewish legal prohibition should be absolute. There is a unique obligation to prevent youth from obtaining these products. Jewish law might also prohibit deriving benefit from the sale or advertisement of these products.
Conclusions: Extrapolating from rabbinic literature regarding combustible cigarettes, the preliminary data establishing the dangers of e-cigarettes and the government warnings against usage would render these products prohibited under Jewish law, especially for youth and pregnant women.
Objective: The World Health Organization’s (WHO) guidelines for cancer pain management were intentionally made simple in order to be widely implemented by all physicians treating cancer patients. Referrals to pain specialists are advised if pain does not improve within a short time. The present study examined whether or not a reasonable use of the WHO guideline was made by non-pain specialists prior to referral of patients with cancer-related pain to a pain clinic.
Methods: Cancer patients referred to a pain specialist completed several questionnaires including demographics, medical history, and cancer-related pain; the short-form McGill Pain Questionnaire (SF-MPQ); and the Short Form Health Survey SF-12. Data from referral letters and medical records were obtained. Treatments recommended by pain specialists were recorded and categorized as “unjustified” if they were within the WHO ladder framework, or “justified” if they included additional treatments.
Results: Seventy-three patients (44 women, 29 men) aged 55 years (range, 25–85) participated in the study. Their pain lasted for a mean of 6 (1–192) months. Mean pain intensity scores on a 0–10 numerical rating scale were 7 (2–10) at rest and 8 (3–10) upon movement. Most patients complied with their referring physician’s recommendations and consumed opioids. Adverse events were frequent. No significant correlation was found between the WHO analgesic medication step used and mean pain levels reported. There were 63 patient referrals (85%) categorized as “unjustified,” whereas only 11 patients (15%) required “justified” interventions.
Conclusions: These findings imply that analgesic treatment within the WHO framework was not reasonably utilized by non-pain specialists before referring patients to pain clinics.
Objective: The aim of the present study was to determine and compare the expression pattern and localization of nestin, in an attempt to explore its role in oral carcinogenesis.
Methods: Western blot and immunohistochemistry analysis were performed to study the expression pattern of nestin in normal mucosa, leukoplakia, and oral squamous cell carcinoma samples. Nestin expres¬sion was evaluated in the keratinocytes and blood vessels of all the samples and compared with various clinico-pathological parameters.
Results: Nestin expression was increased in samples of leukoplakia and oral squamous cell carcinoma when compared with normal mucosa. Among leukoplakia samples, the expression was increased in cases without dysplasia compared to cases with dysplastic features. In cases of oral squamous cell carcinoma, the expression of nestin was found to be decreased with the loss of differentiation. Neoangiogenesis status determined by nestin expression showed an increasing expression from normal mucosa through leuko-plakia, to oral squamous cell carcinoma.
Conclusion: This study has two major findings: 1) identification of nestin as an effective indicator of neo-angiogenesis, and 2) nestin may be used as a marker in predicting the early changes in oral carcinogenesis.
To the Editor,
I am writing in response to Dr Sharon Galper Grossman’s recent fascinating article, “Vape Gods and Judaism—E-cigarettes and Jewish Law.”1 The author extrapolates from rabbinic literature regard-ing combustible cigarettes and suggests that the preliminary data establishing the dangers of e-cigarettes, and the government warnings against usage, would render these products prohibited under Jewish law, especially for youth and pregnant women.
The development of the modern hospital is usually dated to the nineteenth century. During this time, many municipal and sectarian hospitals were established and developed, and Jewish hospitals were no exception. Such developments also occurred in the Netherlands. This essay describes the different histories of the Jewish hospitals in Rotterdam and The Hague during the nineteenth century. The Rotterdam institution lasted for more than 130 years (until it was closed by the Nazis during the Second World War), whereas the one in The Hague existed for only 31 years. This study will suggest a number of possible explanations for the relatively long and successful history of the Jewish hospital in Rotterdam and the contrastingly brief duration of the Jewish hospital in The Hague.
Background: There is a consensus among the halachic authorities that life-saving actions override Sabbath prohibitions. They are painstaking in securing that the sanctity of the Sabbath is maintained but that not a single life be lost.
Objective: This manuscript examines if and when a relative’s presence at the bedside of a seriously ill individual is potentially life-saving against the backdrop of the scientific literature. It specifically addresses the permissibility of traveling in a motorized vehicle, generally prohibited on the Sabbath, to be with one’s relative in hospital for the provision of emotional support.
Methods: Discourse of the halachic issues in the context of the scientific literature.
Results: Stress, mental or physical, has been determined as a potentially life-threatening condition in many disease entities. The literature attests to both the patient’s and the professionals’ perception of the curative potential of the presence of loved ones by advocating for the patient and relieving stress in the hospital experience. Emotional support from a loved one is perceived by some patients as vital to survival. There is halachic consensus that a patient’s perception of the emotional need for a relative’s presence is sufficient to permit overriding rabbinic prohibitions. Torah prohibitions, which may be overridden for medical needs, may be overridden for emotional support, providing a health professional or family member attests to the fulfilment of this specific need as diminishing the danger to the patient’s life. In certain cases, the latter contingency is unnecessary.
Conclusions: Emotional support has an impact on the patient’s health status; the degree to which its impact is strong enough to save life is still being studied. As more data from scientific studies emerge, they may be relevant to sharpening the halachic rulings with respect to the issue at hand.
