Carrier State Research Articles

Advances in the understanding, detection and management of equine strangles

SummaryStreptococcus equi subspecies equi (S. equi) is the causative organism of the upper respiratory disease of equids, strangles, characterised by pyrexia, lymphadenopathy and mucopurulent nasal discharge. Strangles was first reported over 750 years ago and continues to be of significance in equine populations across the globe. This review discusses how S. equi has adapted, the clinical manifestation of strangles, and how clinicians and caregivers can tackle the disease in the future. S. equi evolved from the commensal, and occasionally opportunistic pathogen, Streptococcus equi subspecies zooepidemicus refining its capabilities as it became host restricted. The success of S. equi can be attributed to its ability to cause both acute and persistent infection, the latter occurring in about 10% of those infected. In this carrier state, S. equi persists in the guttural pouch without causing clinical signs, intermittently shedding into the environment, and encountering naïve animals. Insight into the S. equi genome and lifestyle has led to advances in diagnostic assays and the development of a safe and efficacious recombinant‐fusion vaccine, giving clinicians and caregivers the tools to better combat this infection. Alongside rigorous biosecurity protocols and pragmatic control measures such as screening new arrivals for exposure and carrier status, these new technologies demonstrate that strangles can be an increasingly preventable infection.

Dependence of the tunneling properties on an anisotropic factor in a graphene-like system

In analogy with the Klein tunneling in an isotropic linear energy graphene system, we reveal an anisotropic Klein tunneling in an anisotropic two dimensional (2D) linear energy system. The chirality and the absence of the back scattering leads to the Klein tunneling. The tunneling characteristics can be tuned by the barrier structure, the incident energy and angle, and more importantly the anisotropic parameter and different potential direction. The controllable Klein and side tunneling peaks can be understood by the carrier states and the phases in barrier/well regions. This interesting tunneling behaviors enrich the 2D tunneling properties and broaden the studies on the three-dimension tunneling features which will enlarge its electronic applications.

Temperature-dependent carrier state mediated by H-NS promotes the long-term coexistence of Y. pestis and a phage in soil.

The study of carrier state phages challenged the canonical lytic-lysogenic binary, and carrier state appears to be ubiquitous and ecologically important. However, the mechanisms of the carrier state are not well elucidated due to the limited phage models. Herein, we reported phage HQ103, similar to Escherichia coli phage P2. In contrast to the temperate P2 phage, the HQ103 phage does not insert its genome into the bacterial chromosome and displays a dual behavior depending on the temperature. At 37°C, HQ103 lyses the host and forms clear plaques due to the truncation of repressor CI and mutation of promoter Pc. In contrast, HQ103 maintains a carrier state lifestyle with Y. pestis at an environmental temperature (21°C). Mechanistically, we found that the host-encoded histone-like nucleoid-structuring protein H-NS, which is highly expressed at 21°C to silence the Cox promoter Pe and inhibits the phage lytic cycle. Subsequently, the HQ103 carrier state Y. pestis could grow and co-exist with the phage in the soil at 21°C for one month. Thus, this study reveals a novel carrier state lifestyle of phage HQ103 due to the H-NS mediated xenogeneic silencing and demonstrates that the carrier state lifestyle could promote long-term phage-host coexist in nature.

Prevention of surgical site infections: a personal odyssey

Prevention of surgical site infections: a personal odyssey

Clotting Factor Deficiencies as an Underlying Cause of Abnormal Uterine Bleeding in Women of Reproductive Age: A Literature Review.

Clotting Factor deficiencies are rare disorders with variations in clinical presentation and severity of symptoms ranging from asymptomatic to mild to life-threatening bleeding. Thus, they pose a diagnostic and therapeutic challenge, mainly for the primary health care providers, general practitioners, and gynecologists who are more likely to first encounter these patients. An additional diagnostic challenge arises from the variable laboratory presentations, as PT, PTT, and BT are not always affected. The morbidity is higher among women of reproductive age since Abnormal Uterine Bleeding-specifically Heavy Menstrual Bleeding-is one of the most prevalent manifestations of these disorders, and in some cases of severe deficiencies has led to life-threatening episodes of bleeding requiring blood transfusions or even immediate surgical intervention. Physician awareness is important as, in the case of some of these disorders-i.e., Factor XIII deficiency-prophylactic treatment is available and recommended. Although uncommon, the potential for rare bleeding disorders and for hemophilia carrier states should be considered in women with HMB, after more prevalent causes have been excluded. Currently, there is no consensus on the management of women in these instances and it is reliant on the physicians' knowledge.

Performance Improvement of InGaN-Based Red Light-Emitting Diodes via Ultrathin InN Insertion Layer

The serious separation of electron–hole wavefunctions, which is caused by the built-in electric field, prevents electron–hole radiative recombination in quantum wells (QWs) in high-In-content InGaN-based red light-emitting diodes (LEDs). Here, we propose a staggered structure that inserts an ultrathin InN layer in the single quantum well (SQW) to reduce the piezoelectric polarization and suppress the quantum confined Stark effect (QCSE). We have numerically simulated the effects of SQW with the InN insertion layer (IL) on the energy band structure and electron–hole wavefunctions of the red LED. Owing to alleviated piezoelectric polarization and improved overlaps of electron–hole wavefunctions, the simulation results have revealed that the internal quantum well (IQE) of the red LED with InN IL exhibits 42% higher than that of the red LED with a square-shaped QW (SSQW) at 60 A/cm2, and the efficiency droop ratio of red LED with InN IL is 48% lower than that of red LEDs with SSQW. Furthermore, we have found that the position of InN IL can affect the energy states of carriers, which has a great influence on the IQE and peak emission wavelength of red LEDs.

Monitoring for Equine Viral Arteritis has decreased its prevalence in European breeding sires

Equine viral arteritis (EVA) can induce a persistent carrier state in stallions and shedding of the virus with semen can spread EVA and cause abortions in seronegative pregnant mares. In the early 1990s, obligatory testing for EVA of stallions used for artificial insemination was implemented within the European Union (Council Directive 92/65/EEC). In addition, vaccination programs for young stallions and exclusion of carrier stallions from certain breed registry events were implemented in Warmblood sport horses. Information on the efficacy of these actions on the prevalence of EVA in reproductively active stallions are not yet available in Europe. This study retrospectively analyzed results of serological and virus antigen testing for EVA in sires (n=308, one sample set per sire, EVA-vaccination status unknown) of different age and breed referred to the Centre for Artificial Insemination of Vetmeduni Vienna for semen preservation between 2001 and 2021. For analysis, stallions were grouped by age (1-3, 4-10, 11-16, >16 years) and breed. The EVA antibody titer was determined by serum neutralization test and semen was analyzed for EVA virus by PCR and/or virus isolation test. Statistical analysis was performed by chi2-test, Kruskal-Wallis test or Mann-Whitney U-test using the IBM SPSS 28.0 statistics software. Of 308 stallions tested, 14.9% (n=46) were EVA seropositive and in 12 stallions EVAvirus was detected in semen (26% of seropositive and 3.8% of all tested stallions, respectively). The incidence of seropositive stallions (22% of sires tested during 2001-05 to 4.1% during 2016-21) and of stallions shedding EVA virus via semen (8.5% of all serologically tested stallions 2001-05 to 1.4% during 2016-21) decreased over time (p<0.05). No difference among breeds with regard to occurrence of seropositive stallions was detected. There was a tendency towards more Standardbred and Lipizzaner stallions (14% and 13%, respectively) shedding EVA virus in semen compared to all other breeds (<3%, p=0.074 among groups). Differences in the seroprevalence of EVA antibodies existed among stallions from different age groups (p<0.01) with the highest percentage of seropositive stallions in 11-16 year-stallions (45.7%). No differences among age groups with regard to virus shedding existed. The EVA antibody titer increased with age (p<0.01), reflecting a higher possibility of repeated virus challenge in older stallions. Antibody titer was not associated with carrier state. In conclusion, monitoring of stallions for EVA in combination with vaccination programs resulted in a decrease of the prevalence of seropositive and virus-shedding stallions during the past 20 years in a European stallion population and can therefore be considered successful.

A CROSS-SECTIONAL STUDY TO FIND OUT THE PROPORTION OF HEPATITIS B VIRUS INFECTION AND ITS ASSOCIATED RISK FACTORS AMONG PREGNANT WOMEN ATTENDING ANTENATAL CLINIC IN TERTIARY HEALTH CARE CENTER IN CENTRAL INDIA

Background: Hepatitis B virus (HBV) infection continues to be a life- threatening health problem throughout world, infecting more than two billion people. While blood transfusion and unsafe therapeutic injection continue to be major risk factors, the role of vertical transmission remains under- estimated. Hence, this study was done to nd out the prevalence of HBV infection and associated risk factors among healthy pregnant women in Central India Indore (M.P.). The present study was a prospective, cross-sectional study conducted, in the department of Microbiology of M.G.M. Medical College from June 2021 to June 2022. Methodology: After receiving 5 ml of blood sample in the Microbiology Laboratory, serum was separated by centrifugation. They were then tested for Hepatitis B surface antigen (HBsAg) by Rapid Test and Enzyme linked Immunosorbent assay (ELISA). Results: Total 610 samples were screened among which 12 (%) were tested positive for HBsAg. Pregnant women found with history of blood transfusion was found to be 5(41.66%), followed by tattooing which was 33.33%, followed by history of multiple sexual partners, HIV positive and family history of HBV infection which was 8.33%,8.33% and 8.33% respectively. Conclusion: Perinatal transmission is the major route of HBV transmission in the absence of prophylaxis, a large proportion of viremic mothers transmits infection to neonates. Immunization is the most effective and only way of preventing development of chronic carrier state. Hence all neonates were administered with hepatitis B vaccine and 0.5 ml of hepatitis B immunoglobulin within 12 hours of birth

Management of the Sickle Cell Trait: An Opinion by Expert Panel Members.

The number of individuals with the sickle cell trait exceeds 300 million worldwide, making sickle cell disease one of the most common monogenetic diseases globally. Because of the high frequency of sickle cell disease, reproductive counseling is of crucial importance. In addition, unlike other carrier states, Sickle Cell Trait (SCT) seems to be a risk factor for several clinical complications, such as extreme exertional injury, chronic kidney disease, and complications during pregnancy and surgery. This expert panel believes that increasing knowledge about these clinical manifestations and their prevention and management can be a useful tool for all healthcare providers involved in this issue.

44 Detecting conformational differences in Fragile Foal Syndrome carriers utilizing artificial intelligence

Conformation traits impact gait and performance, and as a result vary based on intended use of the horse. For example, a horse with longer legs can cover a greater distance per stride than one with shorter legs. Limb length, therefore, is advantageous for horses expected to travel long distances for extended periods of time but may not be for those who go short distances at top speeds. Fragile Foal Syndrome (FFS) in horses results from a sequence change in PLOD1, the same gene that causes Ehlers Danlos Syndrome type IV (EDS-IV) in humans, a condition that results in longer limbs. Based on the phenotype observed in EDS, we hypothesize that FFS in the carrier state may impact extremity length including the neck, forelimbs, and hindlimbs in horses. To measure conformation parameters, we first digitally labeled specific anatomical points on a video recording of a trotting horse using the software package DeepLabCut (DLC). Representative frames for each horse at the same point within the stride were extracted from the video. The X, Y coordinates of each anatomical label were used to quantify conformation geometry. Frame extraction was done with a custom designed graphical interface that ensured the user could identify the ideal frame matching an identical body position across all horses examined. X,Y coordinate output files were thenanalyzed with a custom gait parameter pipeline written in MatLab to calculate the neck, forelimb, and hindlimb length. Each measurement was scaled to account for the varying distance horses were from the camera. Pulled tail hair was utilized to extract DNA and genotype each horse using PCR-RFLP, then followed by Sanger Sequencing for confirmation. Conformational measures were compared between genotype categories (wild type vs, carrier) in JMP Pro. Preliminary results showed that FFS carriers (n = 7) had significantly longer forelimb (P = 0.0344, t-test), hindlimb (P = 0.0258, t-test), and neck (P = 0.0013, t-test) lengths compared with wild type horses (n = 7). Future work will increase the overall sample size and number of frames captured per individual to increase statistical power and allow investigation of more conformation traits including static joint angles and back lengths. Improved understanding of conformational phenotypes that may result from the FFS carrier genotype will inform future studies of equine physiology and connective tissue disorders, leading to better decision making for breeding, sales and training, and preventing injury and loss of foals to this disease.

Primary immunodeficiency with autoimmunity, two facets of same coin?-A novel case with therapeutic dilemma

12 year female born of Grade 2 consanguineous marriage presented with history of painful swelling in the right axilla and neck for 2 months. She also had history of multiple joint pain involving small and large joints with early morning stiffness for 2 months. She had past history of treatment for tubercular cervical lymphadenitis (caseating granuloma in biopsy) at 4 years of age. She was immunized appropriate for her age. Her father and paternal aunt had psoriasis. On examination she had warm and tender subcutaneous swelling 2 × 2 cm in right axilla. Significant lymphadenopathy noted in right cervical and femoral region. Psoriatic plaque was noted over scalp and right retroauricular area.Musculoskeletal examination showed bilateral wrist, ankle arthritis and bilateral achilles tendinitis. On evaluation her hemoglobin 11 mg/dl, WBC count 19000 (N88%, L9%, M3%), platelet 665000 with neutrophilic leukocytosis and shift to left. Ultrasound of right axilla confirmed abscess. Incision and drainage of abscess was done. Pus culture grew S.aureus. She was diagnosed as psoriatic arthritis with axillary abscess and generalized significant lymphadenopathy. In view of abscess, generalized lymphadenopathy, leukocytosis and neutrophilia, PID workup was done. Her immunoglobulin levels were normal. Lymphocyte subset analysis showed reduced CD8+T lymphocytes. NBT activity was seen in 55% of stimulated neutrophils (90% in control sample). DHR assay (test done twice 2 weeks apart) showed markedly decreased Neutrophil oxidative burst. Cervical lymph node biopsy revealed granulomatous inflammation. CBNAAT of sample was negative for tuberculosis. Her genetic workup showed mutation for a novel missense variant c.908T>G in Exon 10 of NCF4 and carrier state in parents and her HLA typing was positive for HLACw6. She was diagnosed as chronic granulomatous disease with psoriatic arthritis. She received sulfamethoxazole/trimethoprim, itraconazole prophylaxis and treatment with methotrexate 7.5 mg/week for arthritis. Discussion1. CGD is associated with few autoimmune manifestations like colitis, arthritis etc. To the best of our knowledge, association with Psoriatic arthritis is not reported. 2. Treatment of our case has unique challenging issues as use of DMARDS for psoriatic arthritis may increase infection chance in preexisting CGD and use of steroids for granuloma may cause rebound flare of psoriasis.

Epidemiological and microbiome associations of Clostridioides difficile carriage in infancy and early childhood

ABSTRACT There has been an increase in the prevalence of Clostridioides difficile (C. diff) causing significant economic impact on the health care system. Although toxigenic C. diff carriage is recognized in infancy, there is limited data regarding its longitudinal trends, associated epidemiolocal risk factors and intestinal microbiome characteristics. The objectives of our longitudinal cohort study were to investigate temporal changes in the prevalence of toxigenic C.diff colonization in children up to 2 years, associated epidemiological and intestinal microbiome characteristics. Pregnant mothers were enrolled prenatally, and serial stool samples were collected from their children for 2 years. 2608 serial stool samples were collected from 817 children. 411/817 (50%) were males, and 738/817 (90%) were born full term. Toxigenic C.diff was detected in 7/569 (1%) of meconium samples, 116/624 (19%) of 2 m (month), 221/606 (37%) of 6 m, 227/574 (40%) of 12 m and 18/235 (8%) of 24 m samples. Infants receiving any breast milk at 6 m were less likely to be carriers at 2 m, 6 m and 12 m than those not receiving it. (p = 0.002 at 2 m, p < 0.0001 at 6 m, p = 0.022 at 12 m). There were no robust differences in the underlying alpha or beta diversity between those with and without toxigenic C. diff carriage at any timepoint, although small differences in the relative abundance of certain taxa were found. In this largest longitudinal cohort study to date, a high prevalence of toxigenic C. diff carrier state was noted. Toxigenic C. diff carrier state in children is most likely a transient component of the dynamic infant microbiome.

Entropy of Coherent States of Optical Fields

We consider statistical mixtures of two and three arbitrary coherent states that are the states of a data carrier in an optical communication channel. The eigenvalues and eigenvectors of the corresponding density operators are obtained in analytic form. For this purpose, an original parameterization of triangles on the complex phase plane is introduced. Analytic expressions are obtained for the von Neumann entropy of mixtures of two and three arbitrary coherent states, and its maximal value for a given average number of photons is calculated. It is found that the use of three coherent states for a given average number of photons ensures a larger capacity of an optical communication channel as compared to two states.

Therapeutic efficacy of enrofloxacin in treatment of Francisella orientalis infections in juvenile Nile tilapia (Oreochromis niloticus L.).

Outbreaks of infections by Francisella orientalis represent one of the main obstacles to Nile tilapia (Oreochromis niloticus L.) farming. It is responsible for acute mortality in fingerlings and juveniles. The main control measure available is oral antibiotic therapy. This study compared the therapeutic efficacy of the antibiotics enrofloxacin and oxytetracycline, the most commonly used antimicrobial, against francisellosis in juvenile Nile tilapia (O. niloticus). Fish were challenged with a virulent isolate of F. orientalis and treated with medicated feed containing one of two doses of oxytetracycline (100 or 300 mg/kg of live weight (LW)) or 10 mg/kg of LW of enrofloxacin. The positive and negative control groups received feed without antibiotics; the negative control group was unchallenged. The results showed that enrofloxacin at a dose of 10 mg/kg of LW is effective against francisellosis in juvenile Nile tilapia (O. niloticus). Treatment with oxytetracycline did not eliminate the pathogen from the infected host, and the surviving fish became carriers. Enrofloxacin was able to cure the fish of infection with F. orientalis. This study suggests that enrofloxacin is a better option for treating francisellosis in Nile tilapia (O. niloticus L.). It controls mortality and avoids the carrier state in the fish, thus reducing the possibility of recurrence in the affected batches.

Rapid Decline Rather Than Absolute Level of HBsAg Predicts Its Seroclearance in Untreated Chronic Hepatitis B Patients From Taiwanese Communities.

Hepatitis B surface antigen (HBsAg) clearance leads to favorable outcomes in patients with chronic hepatitis B. HBsAg levels <200 IU/mL with HBsAg decline >0.5 log 10 IU/mL in 1 year have been reportedly predictive of HBsAg loss. This study aimed to use the REVEAL-hepatitis B virus cohort to validate and simplify this prediction rule and verify whether the simplified algorithm can be used among various clinical subgroups. We analyzed 707 patients with untreated chronic hepatitis B who had 3 or more HBsAg measurements within 5 years before HBsAg seroclearance or last visit, greater than 1 year apart from one another. Rapid HBsAg decline was defined as HBsAg decline >0.5 log 10 IU/mL in 1 year or >1 log 10 IU/mL in 2 years. Sensitivity, specificity, positive predictive values, and negative predictive values were compared to assess the predictability of HBsAg seroclearance. During a median follow-up of 10.7 years, 41 of the 707 patients cleared serum HBsAg. HBsAg levels at all measurements were lower ( P < 0.0001) and HBsAg decline was greater ( P < 0.0001) in patients with seroclearance compared with non-seroclearance patients. The predictive accuracy of predicting 1-year HBsAg loss using only the rapid decline algorithm (sensitivity = 0.4412, specificity = 0.9792, positive predictive value = 0.5172, negative predictive value = 0.972) was the same as the model combining rapid HBsAg decline and HBsAg levels <200 IU/mL. The simplified algorithm including only the rapid decline performed similarly among various levels of HBsAg, hepatitis B virus DNA, and alanine aminotransferase and was independent of inactive carrier state. HBsAg decline >0.5 log 10 IU/mL/yr was a practical predictor of HBsAg seroclearance within 1 year in our community-based untreated cohort.

Determination of CN deep donor level in p-GaN with heavy Mg doping via a carrier statistics approach

An equilibrium carrier statistics approach with a partial ionization model is proposed to determine the energy level of CN deep donors in p-type GaN with heavy Mg doping. Unlike usual compensating centers that are assumed to be fully ionized under equilibrium, partial ionization of the CN donor was taken into consideration. The energy level of the CN donor is determined to be EV + (0.20 ± 0.01) eV at elevated temperatures (∼350 K) using such a partial ionization model. The donor level for an isolated C center at a low temperature limit is further calculated considering the doping and temperature effects, which is EV + (0.32 ± 0.01) eV. Furthermore, the ionization ratio of CN is found to be dependent on the C concentration and can then be estimated to be in the range of 0.3–0.8. Such a partial ionization characteristic of CN may capture/emit free carriers during device operation and should be taken into account when analyzing device reliability.

Many-body bound states and induced interactions of charged impurities in a bosonic bath

Induced interactions and bound states of charge carriers immersed in a quantum medium are crucial for the investigation of quantum transport. Ultracold atom-ion systems can provide a convenient platform for studying this problem. Here, we investigate the static properties of one and two ionic impurities in a bosonic bath using quantum Monte Carlo methods. We identify three bipolaronic regimes depending on the strength of the atom-ion potential and the number of its two-body bound states: a perturbative regime resembling the situation of a pair of neutral impurities, a non-perturbative regime that loses the quasi-particle character of the former, and a many-body bound state regime that can arise only in the presence of a bound state in the two-body potential. We further reveal strong bath-induced interactions between the two ionic polarons. Our findings show that numerical simulations are indispensable for describing highly correlated impurity models.

Progress of CRISPR-Cas9 in Treatment of β-thalassemia

β-thalassemia is a common genetic blood disorder, including three clinical and hemtological conditions: the thalassemia intermedia, β-thalassemia carrier state, and thalassemia major. It is widely distributed in the tropical, subtropical and mediterranean regions, and It has grown to be a significant global public health issue. Currently, the sole curative treatment for β-thalassemia is hematopoietic stem cell transplantation (HSCT), but the development of the HSCT is limited by the lack of an immunomatched donor and the high cost. Considering the advancement of gene editing technology in recent years, it is possible to cure the β-thalassemia with low cost and higher chances of surviving. CRISPR-Cas9 system, since its characteristics of simple operation, targeting specificity and low price, has been widely used in the field of life science and medical science. Currently, the study of CRISPR-Cas9 technology in the treatment of β-thalassemia has made a partial progress. This review systematically introduces the application of CRISPR-Cas9 technology in the treatment of β-thalassemia.

Optimising the screening for haemoglobinopathies in pregnancy planning

Haemoglobinopathies are among the most common inherited disorders around the world. In the United States the diagnosis of haemoglobinopathy or a carrier state is made by universal newborn screening. However, many individuals of childbearing age do not know they are a haemoglobinopathy carrier. Screening for common haemoglobinopathies is generally offered as a part of pregnancy planning so that prospective parents can be counselled regarding the risk of having a child with a haemoglobinopathy. Multiple tests exist to screen patients for presence of haemoglobinopathy carrier or disease state; however, it is crucial to order and interpret the results correctly to appropriately counsel couples. In this case series, we describe clinical scenarios where prospective parents were surprised to unexpectedly have a child with sickle cell disease, a haemoglobinopathy that causes severe clinical complications. Through these cases we demonstrate that deficiencies in testing can occur at different levels which may lead to incorrect estimation of the risk of having a child affected by a haemoglobinopathy. Consultation with a haematologist, laboratory medicine specialist, or genetic counsellor should be considered to select the appropriate test and interpret its results.

Estimating the upper limit of the thermoelectric figure of merit in n- and p-type PbTe

Lead Telluride-based materials are the best alloys for the fabrication of medium-temperature thermoelectric (TE) converters. Even if the outstanding TE performance has been already reported for the n- and p-type PbTe, it is still unknown the highest achievable limit of the figure of merit, that can be produced by this material. Considering the particularities of band structure and degenerate statistics of charge carriers, we calculated the dimensionless thermoelectric figure of merit ZT as a function of the chemical potential of electrons for n- and p-type PbTe. The lower bound estimate of ZTmax gives the value ZTmax ≈ 2 for n-PbTe and ZTmax ≈ 3 for p-PbTe. The model proposed considers the most probable scattering mechanisms in PbTe, such as scattering due to the deformation potential of acoustic (DA) and optical phonons (DO), polarization scattering due to optical phonons (PO), scattering due to the short-term potential of defects (SP), and scattering due to ionized impurity atoms (ID). The possibility of increasing the ZT parameter through the dominant scattering of carriers at the ionized impurities are analyzed. The optimal values of chemical potential μ required for the highest possible dimensionless thermoelectric figure of merit ZT are accurately determined for n- and p-type PbTe. This work says that the potential of PbTe as a thermoelectric material has not been fully realized yet and the ZT parameter for this material can be further enhanced beyond the reported experimental values.