Assessing parosmia patients: a study on the evaluation method using a self-administered odor questionnaire for parosmia.

BACKGROUND: Parosmia symptoms are difficult to quantify due to their heterogeneity among patients, and thus a clinical challenge. This study aimed to assess parosmia with Self-Administered Odor Questionnaire for Parosmia (SAOQ-P), a modification of the widely used SAOQ in Japan. The primary objective was to assess the effectiveness of SAOQ-P in identifying parosmia symptoms and its potential integration into the clinical assessment process. The study also explored traditional olfactory test differences between patients with and without parosmia. METHODS: Patients at Jikei Smell Clinic that presented between May 2022 and November 2022 were recruited and administered the SAOQ-P, which had an added question about changes in the perception of 20 daily odors compared to the original SAOQ. Traditional olfactory tests utilized T&T olfactometry and Open Essence. RESULTS: Of 279 patients, 81 had parosmia, while 198 did not exhibit parosmic symptoms. Parosmia prevalence was influenced by the cause of olfactory dysfunction, with post-infectious and post-COVID-19 patients showing higher parosmia rates. Among parosmia patients, 87% reported changes in their perception of at least one odor assessed by SAOQ-P, with coffee, stool, and perfume most commonly affected. Traditional olfactory tests showed no significant differences between parosmia and non-parosmia groups. The number of odors causing parosmia was negatively correlated with age. CONCLUSION: SAOQ-P offers a promising approach to assess and quantify parosmia symptoms, seamlessly integrating into clinical assessments. SAOQ-P identified parosmia in 87% of patients and revealed insights into triggering factors. Traditional olfactory tests' limitations underscore the need for more accurate, patient-centric diagnostic approaches for parosmia.

Maturation of odour identification ability and related factors in children.

BACKGROUND: Olfaction plays an important role in our daily and social lives, both as adults and as children. This study assessed whether the ability to identify odours increases with age, as well as the ability in various age groups and the factors involved. METHODS: The survey was performed in 2017 on 697 Japanese children (366 girls and 331 boys) aged 6â€"18 years who lived in Tsunan, Niigata Prefecture, Japan by using the 'Open Essence', a card-type odour identification test. We collected information regarding age, sex, and physical characteristic. We also inquired whether participants had siblings or if members of the family smoked, and whether they had conversations about odour at home. Statistical analysis was performed to evaluate the factors affecting odour identification abilities. RESULTS: The results showed that the odour identification abilities of children increase with age, and children who have daily conversations about odours at home have better odour identification abilities. CONCLUSIONS: Odour identification ability increases with age. In addition, our findings suggest that conversation may positively affect odour identification. Hence, it is important for children to be exposed to an environment where they develop an interest in smells for better growth of their olfactory identification ability.

CROSSTALK BETWEEN VITAMIN B AND IMMUNITY.

Vitamin B1 (thiamin) is considered to be the oldest vitamin and in 1936 R.R. Williams and colleagues determined its chemical structure and were able to synthesize this vitamin. Vitamin B1 influences pro-apoptotic proteins, mitochondrial membrane potential, cytochrome C release, protein kinases, p38-MAPK, suppresses oxidative stress-induced NF-kappaB and has anti-inflammatory properties. Deficiency of vitamin B1 may cause beriberi, dysfunction of the nervous system, neuroinflammation, T cell infiltration, chemokine CCL2 activation, over expression of proinflammatory cytokines, such as IL-1, TNF, IL-6, and arachidonic acid products, and induces expression of CD40 by the microglia and CD40L by astrocytes which provoke the death of neurons. Here we report the relationship between vitamin B complex and immunity.

Can vitamin a mediate immunity and inflammation?

Vitamins are natural components of foods and are organic compounds distinct from fat, carbohydrates and proteins. Vitamin A is the generic descriptor for compounds with the qualitative biological activity of retinol. Unlike beta-carotene, vitamin A is not an antioxidant and its benefit is related to possible boosting of immune reactions. The effect of vitamin A on immune function is wide-reaching and its deficiency appears to affect immunity in several ways. Innate and adaptive immune responses are affected in some way by lack of vitamin A. Retinoids seem to act on differentiation of lymphocytes, antibody production, phagocytosis of macrophages, NK, Treg, and T helper cell activity. In addition, in humans, signs of a vitamin A deficiency also include the dysregulation of cytokine/chemokine generation and release. However, excess of vitamin A has been demonstrated to have toxic effects in most species studied. Here we summarize some important effects of vitamin A in immunity and inflammation.

Comparison of perioperative and short-term oncological outcomes after single- or multiport surgery for colorectal cancer.

AIM: The aim of this retrospective study was to compare the short-term surgical results of single-port surgery (SPS) with those of multiport surgery (MPS) for colorectal cancer. METHOD: We studied 673 consecutive patients who underwent SPS or MPS for colorectal cancer in our department from January 2008 to December 2013. The operative parameters and oncological outcome were analysed and compared between the SPS and the MPS groups retrospectively. RESULTS: The SPS and MPS groups did not differ significantly in terms of preoperative evaluation. The median operative time was significantly shorter with SPS than with MPS (176 min vs 193 min; P < 0.001). The two groups did not differ significantly in terms of postoperative complications. Length of hospital stay was significantly shorter with SPS than with MPS (8 days vs 10 days; P < 0.001). Oncological resection was similar in the two groups. The disease-free survival rates at 2 years according to the TNM stage did not differ significantly between the two groups (Stage I, 98.5% vs 94.7%; Stage II, 93.4% vs 90.7%; and Stage III, 70.8% vs 68.4%). CONCLUSION: Our experience demonstrates that SPS is safe and can provide oncological outcomes equal to those of MPS in patients with colorectal cancer.

Experimental transmission of AA amyloidosis by injecting the AA amyloid protein into interleukin-1 receptor antagonist knockout (IL-1raKO) mice.

The incidence of AA amyloidosis is high in humans with rheumatoid arthritis and several animal species, including cats and cattle with prolonged inflammation. AA amyloidosis can be experimentally induced in mice using severe inflammatory stimuli and a coinjection of AA amyloid; however, difficulties have been associated with transmitting AA amyloidosis to a different animal species, and this has been attributed to the "species barrier." The interleukin-1 receptor antagonist knockout (IL-1raKO) mouse, a rodent model of human rheumatoid arthritis, has been used in the transmission of AA amyloid. When IL-1raKO and BALB/c mice were intraperitoneally injected with mouse AA amyloid together with a subcutaneous pretreatment of 2% AgNO3, all mice from both strains that were injected with crude or purified murine AA amyloid developed AA amyloidosis. However, the amyloid index, which was determined by the intensity of AA amyloid deposition, was significantly higher in IL-1raKO mice than in BALB/c mice. When IL-1raKO and BALB/c mice were injected with crude or purified bovine AA amyloid together with the pretreatment, 83% (5/6 cases) and 38% (3/8 cases) of IL-1raKO mice and 17% (1/6 cases) and 0% (0/6 cases) of BALB/c mice, respectively, developed AA amyloidosis. Similarly, when IL-1raKO and BALB/c mice were injected with crude or purified feline AA amyloid, 33% (2/6 cases) and 88% (7/8 cases) of IL-1raKO mice and 0% (0/6 cases) and 29% (2/6 cases) of BALB/c mice, respectively, developed AA amyloidosis. These results indicated that IL-1raKO mice are a useful animal model for investigating AA amyloidogenesis.

Impact of mast cells on multiple sclerosis: inhibitory effect of natalizumab.

Mast cells (MCs) derive from a distinct precursor in the bone marrow and are predominantly found in tissues at the interface between the host and the external environment where they can secrete mediators without overt degranulation. Mast cells mature under local tissue microenvironmental factors and are necessary for the development of allergic reactions, through crosslinking of their surface receptors for IgE (FcεRI), leading to degranulation and the release of vasoactive, pro-inflammatory and nociceptive mediators that include histamine, pro-inflammatory and anti-inflammatory cytokines and proteolytic enzymes. Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demylination within the central nervous system. MCs are involved in the pathogenesis of MS by generating various vasoactive mediators and cytokines and participate in the destruction of the myelin sheath and the neuronal cells. The process of the development of demyelinating plaques in MS is probably linked with the rupture of the blood-brain barrier by MC products. The effects of natalizumab, which is a very effective drug in reducing the annualized relapse rate and other relapse-based endpoints, are discussed. Here, we report the relationship between MCs and MS.

Corticotropin-releasing hormone, microglia and mental disorders.

Microglia derive from mononuclear myeloid progenitors and are a major glial complement of the central nervous system. When microglia are activated they secrete inflammatory cytokines and toxic mediators which amplify the inflammatory response. In addition, the microglia inflammatory products are implicated in the neuronal destruction usually observed in various neurodegenerative diseases. Microglia cells express corticotropin releasing hormone (CRH) receptors, and activation of microglia by CRH releases bioactive molecules which have a biological effect in the brain and regulate several neurological diseases. CRH plays a pivotal role in stress responses and is a key mediator of the hypothalamic-pituitary-adrenocortical system. CRH is expressed in human mast cells, leading to autocrine effects and participates in inflammatory response together with neuropeptides, and stimulates mast cells. IL-33-activated mast cells release vascular endothelial growth factor in response to CRH and act synergistically to increase vascular permeability. CRH also up-regulates IL-18 expression by increasing intracellular reactive oxygen in microglia cells. Here we report the relationship between CRH, microglia and mental disorders.

Nerve growth factor interactions with mast cells.

Neuropeptides are involved in neurogenic inflammation where there is vasodilation and plasma protein extravasion in response to this stimulus. Nerve growth factor (NGF), identified by Rita Levi Montalcini, is a neurotrophin family compound which is important for survival of nociceptive neurons during their development. Therefore, NGF is an important neuropeptide which mediates the development and functions of the central and peripheral nervous system. It also exerts its proinflammatory action, not only on mast cells but also in B and T cells, neutrophils and eosinophils. Human mast cells can be activated by neuropeptides to release potent mediators of inflammation, and they are found throughout the body, especially near blood vessels, epithelial tissue and nerves. Mast cells generate and release NGF after degranulation and they are involved in iperalgesia, neuroimmune interactions and tissue inflammation. NGF is also a potent degranulation factor for mast cells in vitro and in vivo, promoting differentiation and maturation of these cells and their precursor, acting as a co-factor with interleukin-3. In conclusion, these studies are focused on cross-talk between neuropeptide NGF and inflammatory mast cells.

Role of mast cells in atherosclerosis: a classical inflammatory disease.

Atherosclerosis is an inflammatory disease and hyperlipidaemia is one of the main risk factors for aging, hypertension and diabetes. Variance in plasma LDL cholesterol concentration may be associated with differences in cardiovascular disease risk and high levels of lipids are associated with increased risk of developing atherosclerosis. Macrophages, which generate pro-inflammatory cytokines, mainly interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-alpha), are deeply involved in atherosclerosis, as well as mast cells which generate several cytokines, including IL-6 and IFN-gamma, and chemokines such as eotaxin, MCP-1 and RANTES involved in monocyte recruitment and differentiation in the arterial wall. In addition, mast cells participate in lipid retention and vascular cell remodeling, and are mediators of innate and adaptive immunity during atherosclerosis. Mast cells which accumulate in the human arterial intima and adventitia during atherosclerotic plaque progression, release vasoactive and angiogenic compounds, and pro-inflammatory mediators, such as arachidonic acid metabolites, histamine, cytokines/chemokines, platelet activating factor (PAF) and proteolytic enzymes. Mast cells can be activated by pro-inflammatory stimuli, including cytokines, hypercholesterolemia, and hyperglycemia, and trigger the endothelial expression of adhesion molecules such as P-selection, vascular cell adhesion molecule-1 (VCAM-1) and chemokines which mediate the recruitment and adhesion of leukocytes. The participation of mast cells in atherosclerosis is still an enigma and it may be of therapeutic interest to clarify this process.

Relationship between serotonin and mast cells: inhibitory effect of anti-serotonin.

Serotonin (5-HT) is an important neurotransmitter that acts in both central and peripheral nervous system, and has an impact on cell proliferation, migration and apoptosis. 5HT exerts its effects via several receptors. Treatment with anti-5-HT receptors diminish the severity of contact allergy in experimental animals, an effect mediated by mast cells; while an agonist reduces the stress level and relieves pruritus in patients with atopic dermatitis. Mast cells are important for both innate and adaptive immunity and they are activated by cross-linking of FceRI molecules, which are involved in the binding of multivalent antigens to the attached IgE molecules, resulting in a variety of responses including the immediate release of potent inflammatory mediators. Serotonin is present in murine mucosal mast cells and some authors reported that human mast cells may also contain serotonin, especially in subjects with mastocytosis. Here we report the interrelationship between mast cells, serotonin and its receptor inhibitor.

Neuropeptide NGF mediates neuro-immune response and inflammation through mast cell activation.

Human mast cells (first described in 1879 by Paul Ehrlich) develop from committed precursors in the bone marrow expressing the differentiation marker CD34+ and distinct from the three other myeloid cells. Mast cells are present in various tissues especially near blood vessels, epithelia and nerves and they are activated by cross-linking of FcεRI, but also by a number of neuropeptides. NGF mediates a number of inflammatory and autoimmune states in conjunction with an increased accumulation of mast cells which appear to be involved in neuroimmune interactions and tissue inflammation. Here we report some relationships between mast cells and nerve growth factor (NGF).

Interrelationship between IL-3 and mast cells.

It is well established that mast cells, which are found in the tissues in the proximity of small blood vessels and post-capillary venules, play a key role in the early phase of IgE-mediated allergic reactions. A greatly expanded understanding of the biology of IL-3 has emerged since the early 1980s. IL-3 is a specific factor that stimulates the growth of hematopoietic stem and progenitor cells of a variety of lineages and can promote the proliferation of certain classes of lymphocytes distinct from those that are dependent on IL-2. IL-3 has been identified among the most important cytokines for regulation of mast cell growth and differentiation, migration and effector function activities of many hematopoietic cells. IL-3 termed multi colony-stimulating-factor (multi-CSF) or mast cell growth factor (MCGF) is a haematopoietic growth factor which stimulates the formation of colonies for erythroid, megakaryocytic, granulocytic and monocytic lineages. It is predominantly produced by activated T cells, natural killer (NK) cells and mast cells and supports the growth-promoting effects of SCF on mast cell precursors. IL-3 causes severe hypersensivity reactions and plays a pivotal role in exacerbating the inflammatory response in vivo. Here we report the interrelationship between IL-3 and mast cells.

Shape and size of the medial patellofemoral ligament for the best surgical reconstruction: a human cadaveric study.

PURPOSE: The aim of this study was to investigate the shape and the attachments of the medial patellofemoral ligament (MPFL) in cadaver specimens to determine an anatomical basis for the best MPFL reconstruction. METHODS: Twenty fresh-frozen knees were used. Dissection protocol implied performing dissections from within the knee joint. We investigated the shape and the attachments between the MPFL and the quadriceps tendon, the patellar and femur insertions, and all the other relationships with the medial soft tissues of the knee. RESULTS: The distal fibers of MPFL were interdigitated with the deep layer of the medial retinaculum. All isolated ligament had a sail-like shape with the patellar side bigger than the femoral side. The femoral insertion, distinct both from medial epicondyle and adductor tubercle, was located at 9.5 mm (range 4-22) distal and anterior respect to adductor tubercle and proximal and posterior to epicondyle. The medial third of the thickness of patella was involved in the insertion. The proximal third of the patella is always involved in the MPFL attachment; in 45% of the cases, it was extended to the medial third and in one case, an extension at the distal third was found. Additionally in 35% (7 cases), it extended to the quadriceps tendon and it were inconstantly attached at the vastus medialis obliques (VMO) tendon and at the vastus intermedius (VI) tendon in an aponeurotic structure. CONCLUSIONS: The MPFL is a distinct structure that goes from patella to femur with a sail-like shape; its patellar insertion, that mostly occur via an aponeurosis tissue with VMO and VI, is at the proximal third of the patella but it may extend in some cases to the medial third patella or to the quadriceps tendon, or very rarely to the distal third of the patella. In the femoral side, the MPFL is inserted in its own site, in most cases distinct both from epicondyle and adductor tubercle, located on average at a 9.5 mm distance distally and anteriorly in respect to the adductor tubercle. Its lower margin was difficult to define. Given the importance of this structure, it must be reconstructed as anatomically as possible in its insertion and in its shape. Many attempts have been made to make functional reconstructions with less than excellent results.

Impact of mast cells on the skin.

When through the skin a foreign antigen enters it provokes an immune response and inflammatory reaction. Mast cells are located around small vessels that are involved in vasaldilation. They mature under the influence of local tissue to various cytokines. Human skin mast cells play an essential role in diverse physiological and pathological processes and mediate immediate hypersensitive reaction and allergic diseases. Injection of anti-IgE in the skin or other agents that directly activate mast cells may cause the decrease in vascular tone, leakage of plasma and may lead to a fall in blood pressure with fatal anaphylactic shock. Skin mast cells are also implicated as effector cells in response to multiple parasites such as Leishmania which is primarily characterized by its tissue cutaneous tropism. Activated macrophages by IFNgamma, cytotoxic T cells, activated mast cells and several cytokines are involved in the elimination of the parasites and immunoprotection. IL-33 is one of the latest cytokines involved in IgE-induced anaphylaxis and in the pathogenesis of allergic skin disorders. IL-33 has been shown in epidermis of patients with psoriasis and its skin expression causes atopic dermatitis and it is crucial for the development of this disease. Here we review the impact of mast cells on the skin.

Mast cell involvement in rheumatoid arthritis.

Autoimmunity is a failure of self-tolerance resulting in immune reactions against autologous antigen. Rheumatoid arthritis is characterized by inflammation of synovium associated with destruction of the join cartilage and bone. A role of mast cell-mediated inflammation and antibodies are involved in this disease. Numerous cytokines such as IL-1, TNF, IL-8, IL-33 and IFN gamma have been implicated in rheumatoid arthritis and in particular in the synovial joint fluid. Since TNF is believed to activates resident synovial cells to produce collagenase that mediate destruction of cartilage, antagonists against the inflammatory cytokine TNF have a beneficial effects in this disease. Here we review the interrelationship between rheumatoid arthritis and mast cell activation.

Luteolin inhibits mast cell-mediated allergic inflammation.

Mast cells are ubiquitous in the body and multifunctional immune cells; they are known to be primary responders in allergic reactions, orchestrating strong responses to minute amounts of allergens. Mature mast cells perform important beneficial roles in host defense, both in IgE-dependent immune responses to certain parasites and in natural immunity to bacterial infection. In IgE-associated biological responses, the crosslinking of FcεRI-bound IgE with multivalent antigens initiate the activation of mast cells by promoting aggregation of FceRI. This cross-linking receptor-bound IgE by multivalent Ag initiates a cascade of intracellular reactions leading to mediator release such as proinflammatory mediators, chemokines and cytokines. Luteolin belongs to a flavone group of compounds called flavonoids, it has anti-oxidant properties, inhibits some cancer cell proliferation and exerts a regulatory effect on mast cell-mediated inflammatory diseases and allergy. Here we report the impact of luteolin on mast cell activation.

Role of vitamins D, E and C in immunity and inflammation.

Inflammatory responses are operationally characterized by pain, redness, heat and swelling at the site of infection and trauma. Mast cells reside near small blood vessels and, when activated, release potent mediators involved in allergy and inflammation. Vitamin D modulates contraction, inflammation and remodeling tissue. Vitamin D deficiency has been linked to multiple diseases and several data have demonstrated a strong relationship between serum vitamin D levels and tissue function. Therapy targeting vitamin D3 signaling may provide new approaches for infectious and inflammatory skin diseases by affecting both innate and adaptive immune functions. Mast cells are activated by oxidized lipoproteins, resulting in increased expression of inflammatory cytokines and suggesting that the reduction of oxidation of low density lipoprotein by vitamin E may also reduce mast cell activation. Vitamin C is also an anti-oxidant well-known as an anti-scurvy agent in humans. Vitamin C inhibits peroxidation of membrane phospholipids and acts as a scavenger of free radicals and is also required for the synthesis of several hormones and neurotransmitters. In humans, vitamin C reduces the duration of common cold symptoms, even if its effect is not clear. Supplementation of vitamin C improves the function of the human immune system, such as antimicrobial and natural killer cell activities, lymphocyte proliferation, chemotaxis and delayed-type hypersensitivity. Vitamin C depletion has been correlated with histaminemia which has been shown to damage endothelial-dependent vasodilation. However, the impact of these vitamins on allergy and inflammation is still not well understood.

Pain perception in NICU: a pilot questionnaire.

PURPOSE: Neonatal pain management has made a great step forward over the last several years. Despite the drafting of International guidelines, an under-treatment of neonatal pain is still reported. MATERIALS AND METHODS: Medical and paramedical personnel working in five Italian NICUs were asked to complete a questionnaire about pain management. The questionnaire was comprised of three sections: (i) brief explanation of the purpose; (ii) demographic information, including age, profession, religious beliefs, and hospital level; (iii) questionnaire about pain management and prevention. RESULTS: One-hundred and forty caregivers participated in this study. Non-pharmacological analgesia during heel prick or venipuncture was used by 64% and 60% of them, respectively; topical analgesia was performed in 13% of venipunctures; no analgesia was used in 30% of cases for both heel prick and venipuncture. In the case of lumbar puncture, 35% of participants used topical analgesia, 15% non-pharmacological approach, 10% opioids, and 6% intravenous paracetamol. While 65% of participants gave a score of 4 out of 5 about the importance of pain treatment, 39% of them reported that in their department no pain scales were used. CONCLUSIONS: Pain treatment in these NICUs is still far to be optimal. This nonetheless reflects a worldwide trend, which requires more attention on pain prevention, assessment, and treatment.