Negative cavity photon spectral function in an optomechanical system with two parametrically-driven mechanical modes.

We propose an experimentally feasible optomechanical scheme to realize a negative cavity photon spectral function (CPSF) which is equivalent to a negative absorption. The system under consideration is an optomechanical system consisting of two mechanical (phononic) modes which are linearly coupled to a common cavity mode via the radiation pressure while parametrically driven through the coherent time-modulation of their spring coefficients. Using the equations of motion for the cavity retarded Green's function obtained in the framework of the generalized linear response theory, we show that in the red-detuned and weak-coupling regimes a frequency-dependent effective cavity damping rate (ECDR) corresponding to a negative CPSF can be realized by controlling the cooperativities and modulation parameters while the system still remains in the stable regime. Nevertheless, such a negativity which acts as an optomechanical gain never occurs in a standard (an unmodulated bare) cavity optomechanical system. Besides, we find that the presence of two modulated mechanical degrees of freedom provides more controllability over the magnitude and bandwidth of the negativity of CPSF, in comparison to the setup with a single modulated mechanical oscillator. Interestingly, the introduced negativity may open a new platform to realize an extraordinary (modified) optomechanically induced transparency (in which the input signal is amplified in the output) leading to a perfect tunable optomechanical filter with switchable bandwidth which can be used as an optical transistor.

Adoptive cell therapy with induced regulatory T cells normalises the abortion rate in abortion-prone mice.

Ovarian hormones drive invivo generation of regulatory T cells (Tregs) during pregnancy. Little is known about the therapeutic potential of invitro hormone-derived Tregs in pregnancy loss. We investigated the effects of hormone-induced Tregs in a murine model of abortion. CD4+CD25- T cells were isolated from the spleens of CBA/J mice and stimulated with either 17ß-oestradiol (E2), progesterone (P4) or transforming growth factor-ß1 (TGFB1) plus retinoic acid (RA) for 4 days to generate induced Tregs (iTregs). On Days 1-4 of gestation, DBA/2-mated pregnant CBA/J female mice (abortion prone) were injected intravenously with iTregs or Tregs isolated from normal BALB/c-mated pregnant CBA/J mice (np-Tregs). On Day 14, the number of resorbed fetuses was assessed. Serum interferon (IFN)-γ and uterine forkhead box p3 (Foxp3) expression was analysed by ELISA and immunohistochemistry respectively. Using a 3H-thymidine incorporation assay, isolated CD4+CD25+ Tregs induced by the different treatments suppressed the proliferation of CD4+CD25- T cells. Adoptive transfer of iTregs (from all induction groups) significantly decreased fetal resorption in abortion-prone mice. There were no significant changes in serum IFN-γ concentrations after the adoptive transfer of iTregs or np-Tregs. Immunohistochemistry revealed significantly higher Foxp3 expression in gravid uteri from mice injected with np-Tregs and P4-induced iTregs than in the phosphate-buffered saline-treated group. The findings of this study indicate a potential therapeutic benefit of invitro-induced Tregs in patients with recurrent abortion.

Association of SHMT1 gene polymorphisms with the risk of childhood acute lymphoblastic leukemia in a sample of Iranian population.

The enzymes serine hydroxymethyltransferase 1 (SHMT1) regulate key reaction in folate-mediated one-carbon metabolism. In the current study we aimed to examine the possible association between SHMT1 gene polymorphisms and childhood acute lymphoblastic leukemia (ALL) in a sample of Iranian population. The rs9901160, rs2273027, rs9909104, rs1979277, and rs11868708 gene polymorphisms of SHMT1 were genotyped in 120 children diagnosed with ALL and 120 healthy children by the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). The results showed that rs9901160, rs2273027 as well as rs1979277 polymorphism significantly increased the risk of childhood ALL (P<0.05). While, rs9909104 polymorphism significantly decreased the ALL risk (P<0.05). The rs11868708 variant was not associated with risk/protection of childhood ALL (P>0.05). In conclusion, our results suggest that the polymorphisms of SHMT1 gene are associated with childhood ALL risk in a sample of Iranian population. Further studies with larger sample sizes and different ethnicities are necessary to verify our findings.

The burden and management of FXIII deficiency.

Factor XIII congenital deficiency (FXIII CD) is a serious bleeding disorder resulting in a lifelong bleeding tendency, defective wound healing and recurrent miscarriage. The aim of this study was to review available literature on the burden and management of FXIII CD. To this end, Medline, Embase and Cochrane databases were searched. In current literature, FXIII CD is described as one of the most severe forms of a congenital coagulation disorder, primarily due to a high risk of severe bleeding events. The published literature suggests that over 50% of untreated FXIII CD patients experience severe bleeding symptoms. Intracranial haemorrhage (ICH)--a major cause of death and morbidity--is reported to occur in up to one-third of patients. Nonetheless, data on the social and financial burden in patients with FXIII CD are sparse. Identified reports on the effectiveness and safety of recommended treatments support that patients with FXIII CD should receive prophylactic treatment as early as possible in their lives to prevent the occurrence of bleeds, including potentially life-threatening ICHs. In conclusion, limited data on the social and economic consequences related specifically to FXIII CD have been published to date. However, it is widely acknowledged that the high risk of severe bleeds and ICH results in a high level of burden in patients with bleeding disorders. To inform future clinical decision-making and reimbursement decisions, further research is required to gain insight in how specifically FXIII CD affects quality of life and to fully understand associated economic consequences.

Association of P2X7 gene polymorphisms with susceptibility to pulmonary tuberculosis in Zahedan, Southeast Iran.

Susceptibility to tuberculosis may be influenced by variations in human genes. The P2X7 receptor is an ATP-gated cation channel expressed in immune cells, and it influences the release of proinflammatory cytokines from monocytes and macrophages. In the present study, we aimed to evaluate the impact of P2X7 gene rs2393799 (-762T/C) and rs1718119 (Thr348Ala) polymorphisms on patient susceptibility to pulmonary tuberculosis (PTB) in a sample of the Iranian population. This case-control study was performed using 150 PTB cases and 150 controls. P2X7 receptor polymorphisms were determined using tetra-amplification refractory mutation system-polymerase chain reaction. Genotype and allelic frequencies of the rs2393799 variant within the P2X7 gene were significantly higher in the PTB patients than in the healthy controls. The genotypes were CC in 71, CT in 54, and TT in 25 PTB patients. The genotypes were CC in 104, CT in 40, and TT in 6 healthy controls. The results indicate a significant association between rs2393799 polymorphism of the P2X7 gene and susceptibility to PTB (CT vs CC: OR = 6.5, 95%CI = 2.5-16.9, P < 0.0001; TT vs CC: OR = 3.3, 95%CI = 1.2-8.9, P = 0.018; TC+TT vs CC: OR = 2.56, 95%CI = 1.59-4.12, P < 0.0001). The rs2393799 T allele is a risk factor for predisposition to PTB (OR = 2.53, 95%CI = 1.73-3.71, P < 0.0001). No association between the rs1718119 polymorphism and PTB was found. In conclusion, the rs2393799 polymorphism in the P2X7 gene may contribute to patient susceptibility to PTB in our study population.

Successful delivery in patients with FXIII deficiency receiving prophylaxis: report of 17 cases in Iran.

To prevent pregnancy loss in women with severe FXIII deficiency, prophylactic replacement therapy with a source of FXIII throughout pregnancy is essential. The aim of this study was to evaluate the bleeding score and rate of successful deliveries in FXIII-deficient pregnant Iranian women receiving regular prophylaxis. Seventeen FXIII-deficient women 18-35 years old (mean 24 years) were enrolled in the study. All patients except one had a history of at least one miscarriage. Patients received regular prophylaxis with 10 IU kg(-1) FXIII concentrate every 4 weeks before pregnancy and every 2 weeks during pregnancy for a period of 24-62 months. All bleeding episodes were recorded, and the bleeding score was determined on a standard form before and after the start of prophylaxis. After starting prophylaxis, monochloroacetic acid tests and 5 m urea tests were normal in all patients, and the bleeding score significantly decreased from 11-16 (mean 12 ± 1.5) to 23 (mean 2.2 ± 0.4) (P < 0.001). Thirteen minor bleeding episodes occurred during prophylaxis. All patients successfully delivered at 36 weeks' gestation and there were no significant coagulation complications during or after delivery. In this study, successful pregnancy maintenance and delivery were achieved in Iranian women with severe FXIII deficiency. Precise detection and diagnosis of this condition in women with coagulation disorders is essential to enable implementation of appropriate prophylaxis to prevent pregnancy loss.

R620W functional polymorphism of protein tyrosine phosphatase non-receptor type 22 is not associated with pulmonary tuberculosis in Zahedan, southeast Iran.

The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene, which encodes an intracellular lymphoid-specific phosphatase, is considered an important regulator of T-cell activation. We investigated a possible association between the PTPN22 C1858T (R620W) polymorphism and pulmonary tuberculosis in an Iranian population. Single nucleotide polymorphisms of PTPN22 C1858T (rs2476601) were genotyped in 172 pulmonary tuberculosis cases and 204 normal subjects from Zaheden, Iran. Frequencies of genotypes CC, CT and TT of the PTPN22 C1858T polymorphism were 98.3, 1.7 and 0% in the pulmonary tuberculosis patients, and 96.1, 3.9 and 0% in the control group, respectively (P = 0.239). The frequency of the minor (T) allele was 0.8% in pulmonary tuberculosis patients and 2.0% in controls. Significant differences were not observed in genotype or allele frequencies of PTPN22 C1858T in the comparison between pulmonary tuberculosis patients and healthy subjects in our Iranian population sample.

Effect of processing route on the surface properties of amorphous indomethacin measured by inverse gas chromatography.

The aim of this study was to investigate the effect of processing route (i.e., quench cooling and ball milling) on the surface energy heterogeneity and surface chemistry of indomethacin (IMC). Recently developed inverse gas chromatography (IGC) methodology at finite concentrations was employed to determine the surface energy distributions of crystalline, quench cooled and milled IMC samples. Surface properties of crystalline and processed IMC were measurably different as determined by the IGC and other conventional characterization techniques: differential scanning calorimetry and powder X-ray diffraction. Quench cooled IMC was in fully amorphous form. Milled IMC showed no amorphous character by calorimetric or X-ray diffraction studies. It was demonstrated that both processed IMC samples were energetically more active than the crystalline IMC. In particular, milled IMC exhibited a relatively higher dispersive surface energy and higher surface basicity (electron donor capability). This may be attributed to the creation of surface defect sites or exposure of higher energy crystal facets during the milling process. This study confirms that processing route has notable influence on the surface energy distribution and surface acid-base character. IGC was demonstrated as a powerful technique for investigating surface properties of real-world, heterogeneous pharmaceutical materials.

Lack of association between interleukin-18 -607 C/A gene polymorphism and pulmonary tuberculosis in Zahedan, Southeast Iran.

Interleukin-18 (IL-18) plays a critical role in immune response, contributing to the pathogenesis and pathophysiology of infectious diseases. Polymorphisms in the IL-18 genes are known to influence expression levels and may be associated with outcome of infections. The objective of this study was to determine whether the presence of IL-18 polymorphisms -607 A/C (rs1946518) was associated with tuberculosis disease. We investigated the functional polymorphism of IL-18 (rs1946518) in 174 patients with pulmonary tuberculosis (PTB) and 177 healthy subjects. Genotype analysis was done using tetra amplification refractory mutation system-PCR (T-ARMS-PCR). The allelic and genotypic frequencies of the IL-18 polymorphism did not differ significantly between PTB and the controls. Our finding suggests that IL-18 polymorphism (rs1946518) may not be a risk factor for susceptibility to tuberculosis in a sample of Iranian population. Further studies are required to validate our findings.

Molecular basis and prenatal diagnosis of ß-thalassemia among Balouch population in Iran.

OBJECTIVE: To determine the molecular spectrum of ß-thalassemia mutations among at-risk Balouch couples in Iran. METHODS: Mutations' detection in DNAs extracted from the blood of partners of at-risk couples was characterized, and chorion villus sampling by amplification refractory mutation system and DNA sequencing was performed. Fetal diagnosis was also confirmed by linkage analysis. RESULTS: Out of a total of 1234 at-risk Balouch couples referred to the center for prenatal diagnosis (PND) from June 2002 to June 2010, a high percentage of '67.4%' were from consanguineous marriages and 37.4% had between one and four affected children. The trend in referring gradually increased from 34 cases in 2002 to 357 cases in 2010. The astonishing finding was that, unlike most previous studies, only IVS 1-5 with an unusual frequency of 87.20% along with codon 8/9 (+G) with 4% constitutes about 91% of mutations. Altogether, 729 PNDs were made in 583 couples, 25% of whom had over one PND, and surprisingly five PNDs were made in the same woman within just 8 years. CONCLUSION: Regarding the limited types of frequent mutations among Balouch population, it is hopefully believed that the incidence of ß-thalassemia could be controlled by a correct diagnosis in the due time.

Lack of association between rs1024611 (-2581 A/G) polymorphism in CC-chemokine Ligand 2 and susceptibility to pulmonary Tuberculosis in Zahedan, Southeast Iran.

Approximately 5-10% of subjects infected with Mycobacterium tuberculosis develop active tuberculosis. It has been proposed that genetic factors determine the host's vulnerability to tuberculosis. Chemokine (C-C motif) ligand 2 (CCL2), commonly known as monocyte chemoattractant protein-1 (MCP-1), plays a key role in protective immunity against M. tuberculosis. The present study was aimed to determine if there was an association between -2581 A/G single nucleotide polymorphism of CCL2 and pulmonary tuberculosis (PTB) in a sample of Iranian subjects. This case-control study was performed on 142 PTB and 166 healthy subjects. The polymorphism of CCL2 (rs1024611) was determined using tetra amplification refractory mutational system-polymerase chain reaction (tetra ARMS-PCR). There were no significant differences between PTB patients and control subjects regarding -2581 A/G single nucleotide polymorphism of CCL2. In conclusion, our results do not support an association of -2581 A/G polymorphism of CCL2 with PTB susceptibility.

Functional polymorphism of interferon-γ (IFN-γ) gene +874T/A polymorphism is associated with pulmonary tuberculosis in Zahedan, Southeast Iran.

Concerning the key role of interferon-γ (IFN-γ) in the protective immunity against Mycobacterium tuberculosis, we aimed to find the possible association between single nucleotide polymorphism of IFN-γ +874T/A (rs61923114) and pulmonary tuberculosis (PTB). This case-control study was performed on 142 PTB patients and 166 healthy subjects. Genotype analysis was done using amplification refractory mutation system-PCR (ARMS-PCR). We found that the AA genotype of +874A/T IFN-γ is a risk factor for PTB (OR = 3.333, 95% CI = 1.537-7.236, p=0.002). The results showed that the +874A allele frequency was higher in PTB than in normal subjects (OR = 1.561, 95% CI = 1.134-2.480, p=0.007). In conclusion, significant association was found between the IFN-γ +874T/A polymorphism (rs61923114) and susceptibility to PTB in a sample of Iranian population.

Quantitative analysis of taste disorder in COVID-19 patients, the hypersensitivity to salty quality.

Recently, many of the studies have illustrated that the new pandemic SARS-CoV-2 can affect Central Nervous System through the olfactory bulb. In addition to investigating anosmia or hyposmia induced by this virus, a quantitative analysis was needed to clarify the taste and smell disorder of the new coronavirus. The four basic taste quality with five concentrations for sweet, sour, bitter, and salty were administered to 75 subjects divided into three groups: COVID-19 patients with taste disorder, COVID-19 patients without taste disorder, and control group. The results indicated the increment of sweet (2.68 ± 0.14), sour (3.34 ± 0.12) and bitter (3.39 ± 0.2) thresholds in COVID-19 patients with taste disorder in comparison with patients without taste disorder that the threshold were: 2 ± 0.16, 2.11 ± 0.2 and 2.55 ± 0.5 for sweet, sour, and bitter respectively. On the other hand, the patients inversely showed a significant decrease in the salty taste threshold (0.51 ± 0.03) compared to COVID-19 positive control groups (1.11 ± 0.11). Additionally, despite taste disorder in almost all of the patients with smell deficiency, only 30% of cases with taste disorder reported smell deficiency. It may be concluded that some of the taste disorders in patients with COVID-19 disorder could be associated with taste receptors dysfunction or the spread of infection to the cranial nerves responsible for the conduction of tastes sensation.

Ultra-rapid opiate detoxification followed by nine months of naltrexone maintenance therapy in Iran.

INTRODUCTION: The aim of this retrospective study was to assess ultra-rapid opiate detoxification (UROD) and to estimate the retention rate in naltrexone maintenance treatment. METHODS: 45 opiate-addicted male patients (DSM-IV 304.00; opiate per oral or per inhalation n=40, heroin intravenous n=5; concomitant cannabis abuse n=6) were detoxified by 6 h of naloxone infusion under general anesthesia with midazolam, propofol, clonidine and atracurium. Withdrawal signs were evaluated by the objective opiate withdrawal scale (OOWS, range 0-13) up to 24 h after awakening. After UROD, naltrexone 50 mg/day was prescribed for 9 months with assessments in 4-week intervals. RESULTS: Adverse events after UROD were prolonged unconsciousness (n=1), transient confusion (n=8) and depressive mood (n=6). The total sample showed a median OOWS score of 2 (mild withdrawal syndrome). The only two extreme outliers were found only in the subgroups "intravenous" (score 8) and "cannabis" (score 11). 96% (43/45) of the patients could be discharged the day after UROD. Thirty-six patients (80%) continued naltrexone therapy for the entire 9-month observation period. DISCUSSION: UROD and subsequently induction of naltrexone maintenance therapy can be regarded as safe and effective in patients with pure opiate addiction. Owing to cultural and economical factors our Iranian results may not correspond to European and American treatment modalities.

Burden of musculoskeletal disorders in Iran during 1990-2017: estimates from the Global Burden of Disease Study 2017.

Musculoskeletal diseases (MSDs) are the leading cause of disability and facing them demands updated reports on their burden for efficient policymaking. We showed Iran had the highest female-to-male ratio and highest increase in the burden of musculoskeletal diseases, in the past three decades, worldwide. We further confirmed the role of population aging as the main cause. PURPOSE: MSDs comprise most of the top causes of years lived with disability (YLDs) worldwide and are rapidly increasing in lower- and middle-income countries. Here, we present disability and mortality due to MSDs in Iran at the national level from 1990 to 2017. METHODS: We used Global Burden of Disease (GBD) 2017 Study data and standard methodology and presented the burden of MSDs in rates of years of life lost (YLLs), YLDs, and disability-adjusted life years (DALYs) during 1990-2017, for population aged ≥ 5 years old. We further explored attributable risk factors and decomposed the changing trend in DALYs to assess underlying causes. RESULTS: In Iran, MSDs were responsible for 1.82 million (95%uncertainty interval [UI] 1.3-2.4) DALYs, in 2017. During the past 28 years, with 1.75% annualized percentage change (APC), Iran had the highest percentage increase in the all-ages MSD DALYs rate worldwide, while the age-standardized DALYs APC was negligible. Low back pain was the greatest contributor to DALYs and caused 4.5% of total DALYs. The female population is experiencing considerably higher burden of MSDs, with 115% and 48% higher all-ages YLLs and YLDs rates per 100,000, respectively (YLLs 28.7; YLDs 2629.1), than males (YLLs 13.2; YLDs 1766.1). However, due to wide UIs, difference was not significant. Only 17.6% of MSD YLDs are attributable to assessed risk factors. CONCLUSION: Despite that MSDs are rising as an important cause of disability in Iran, these conditions are not sufficiently addressed in health policies. There is urgent need for cross-sectoral engagement, especially addressing the MSDs in females.

Glutaraldehyde test for rapid diagnosis of pulmonary tuberculosis.

OBJECTIVE: To determine the diagnostic value of blood glutaraldehyde gelification time in pulmonary tuberculosis (PTB). DESIGN: We analysed the blood gelification time using 2.5% glutaraldehyde in 83 PTB patients, 46 patients with non-tuberculosis pulmonary disease and 43 healthy subjects. RESULTS: The mean gelification time of PTB patients (556.9 +/- 122.4) is significantly less than non-tuberculosis pulmonary disease (708.0 +/- 100.5) and healthy subjects (821.2 +/- 138.3; P < 0.0001). The optimum cut-off point was 615 seconds by receiver operating characteristic curve analysis. The sensitivity, specificity, positive predictive value and negative predictive value were respectively 85.5%, 89.1%, 93.4% and 77.3% in distinguishing TB from non-PTB patients; and respectively 85.5%, 93.3%, 92.2% and 87.4% in distinguishing PTB patients from controls (non-PTB patients and healthy subjects). CONCLUSION: Because many centres lack sputum culture capacity and sophisticated radiology facilities, the glutaraldehyde test in conjunction with other conventional methods of diagnosis (sputum smear for acid-fast bacilli and frontal chest X-ray) could be a rapid, easy, cost-effective and reliable test for the diagnosis of PTB.