Blue-Detuned Magneto-optical Trap of Molecules.

Direct laser cooling of molecules has reached a phase-space density exceeding 10^{-6} in optical traps but with rather small molecular numbers. To progress toward quantum degeneracy, a mechanism that combines sub-Doppler cooling and magneto-optical trapping would facilitate near unity transfer of ultracold molecules from the magneto-optical trap (MOT) to a conservative optical trap. Using the unique energy level structure of YO molecules, we demonstrate the first blue-detuned MOT for molecules that is optimized for both gray-molasses sub-Doppler cooling and relatively strong trapping forces. This first sub-Doppler molecular MOT provides an increase of phase-space density by 2 orders of magnitude over any previously reported molecular MOT.

Microtubule-associated protein MAP1LC3C regulates lysosomal exocytosis and induces zinc reprogramming in renal cancer cells.

Microtubule-associated protein 1 light chain 3 gamma (MAP1LC3C or LC3C) is a member of the microtubule-associated family of proteins that are essential in the formation of autophagosomes and lysosomal degradation of cargo. LC3C has tumor-suppressing activity, and its expression is dependent on kidney cancer tumor suppressors, such as von Hippel-Lindau protein and folliculin. Recently, we demonstrated that LC3C autophagy is regulated by noncanonical upstream regulatory complexes and targets for degradation postdivision midbody rings associated with cancer cell stemness. Here, we show that loss of LC3C leads to peripheral positioning of the lysosomes and lysosomal exocytosis (LE). This process is independent of the autophagic activity of LC3C. Analysis of isogenic cells with low and high LE shows substantial transcriptomic reprogramming with altered expression of zinc (Zn)-related genes and activity of polycomb repressor complex 2, accompanied by a robust decrease in intracellular Zn. In addition, metabolomic analysis revealed alterations in amino acid steady-state levels. Cells with augmented LE show increased tumor initiation properties and form aggressive tumors in xenograft models. Immunocytochemistry identified high levels of lysosomal-associated membrane protein 1 on the plasma membrane of cancer cells in human clear cell renal cell carcinoma and reduced levels of Zn, suggesting that LE occurs in clear cell renal cell carcinoma, potentially contributing to the loss of Zn. These data indicate that the reprogramming of lysosomal localization and Zn metabolism with implication for epigenetic remodeling in a subpopulation of tumor-propagating cancer cells is an important aspect of tumor-suppressing activity of LC3C.

Sex-specific role of myostatin signaling in neonatal muscle growth, denervation atrophy, and neuromuscular contractures.

Neonatal brachial plexus injury (NBPI) causes disabling and incurable muscle contractures that result from impaired longitudinal growth of denervated muscles. This deficit in muscle growth is driven by increased proteasome-mediated protein degradation, suggesting a dysregulation of muscle proteostasis. The myostatin (MSTN) pathway, a prominent muscle-specific regulator of proteostasis, is a putative signaling mechanism by which neonatal denervation could impair longitudinal muscle growth, and thus a potential target to prevent NBPI-induced contractures. Through a mouse model of NBPI, our present study revealed that pharmacologic inhibition of MSTN signaling induces hypertrophy, restores longitudinal growth, and prevents contractures in denervated muscles of female but not male mice, despite inducing hypertrophy of normally innervated muscles in both sexes. Additionally, the MSTN-dependent impairment of longitudinal muscle growth after NBPI in female mice is associated with perturbation of 20S proteasome activity, but not through alterations in canonical MSTN signaling pathways. These findings reveal a sex dimorphism in the regulation of neonatal longitudinal muscle growth and contractures, thereby providing insights into contracture pathophysiology, identifying a potential muscle-specific therapeutic target for contracture prevention, and underscoring the importance of sex as a biological variable in the pathophysiology of neuromuscular disorders.

Systematic study and uncertainty evaluation of P, T-odd molecular enhancement factors in BaF.

A measurement of the magnitude of the electric dipole moment of the electron (eEDM) larger than that predicted by the Standard Model (SM) of particle physics is expected to have a huge impact on the search for physics beyond the SM. Polar diatomic molecules containing heavy elements experience enhanced sensitivity to parity (P) and time-reversal (T)-violating phenomena, such as the eEDM and the scalar-pseudoscalar (S-PS) interaction between the nucleons and the electrons, and are thus promising candidates for measurements. The NL-eEDM collaboration is preparing an experiment to measure the eEDM and S-PS interaction in a slow beam of cold BaF molecules [P. Aggarwal et al., Eur. Phys. J. D 72, 197 (2018)]. Accurate knowledge of the electronic structure parameters, Wd and Ws, connecting the eEDM and the S-PS interaction to the measurable energy shifts is crucial for the interpretation of these measurements. In this work, we use the finite field relativistic coupled cluster approach to calculate the Wd and Ws parameters in the ground state of the BaF molecule. Special attention was paid to providing a reliable theoretical uncertainty estimate based on investigations of the basis set, electron correlation, relativistic effects, and geometry. Our recommended values of the two parameters, including conservative uncertainty estimates, are 3.13 ±0.12×1024Hzecm for Wd and 8.29 ± 0.12 kHz for Ws.

Analysis of the frequency of single nucleotide polymorphisms in cytokine genes in patients with New Onset Diabetes After Transplant.

New Onset Diabetes After Transplantation (NODAT) is a serious metabolic complication. While ß-cell dysfunction is considered the main contributing factor in the development of NODAT, the precise pathogenesis is not well understood. Cytokines are thought to be involved in the inflammation of islet ß-cells in diabetes; however, few studies have investigated this hypothesis in NODAT. A total of 309 kidney transplant recipients (KTRs) were included in this study. An association between kidney transplants, and the development of diabetes after transplant (NODAT) was investigated. Comparison was made between KTRs who develop diabetes (NODAT cases) or did not develop diabetes (control), using key cytokines, IL-6 G (- 174)C, macrophage mediator; IL-4 C (- 490)T, T helper (Th)-2 cytokine profile initiator; Th-1 cytokine profile initiator interferon-γ T (+ 874) A gene and TGF ß1 C (+ 869) T gene polymorphisms were investigated. The genes were amplified using well-established polymerase chain reaction (PCR) techniques in our laboratory. Compared to the AA and AT genotypes of interferon gamma (IFNG), there was a strong association between the TT genotype of IFNG and NODAT kidney transplant recipients (KTRs) versus non-NODAT KTRs (p = 0.005). The AA genotype of IFNG was found to be predominant in the control group (p = 0.004). Also, significant variations of IL6 G (- 174) C, IL-4 C (- 590) T, interferon-γ T (+ 874) A gene and transforming growth factor ß1 C (+ 869) T may contribute to NODAT. Our data is consistent with theTh-1/T-reg pathway of immunity. Further larger pan Arab studies are required to confirm our findings.

Caudal duplication syndrome in an adolescent: Rare concoction of duplication anomalies.

Caudal duplication syndrome is a rare and interesting entity with a reported prevalence of <1/100,000 births. Caudal duplication syndrome encompasses a diverse spectrum of anomalies primarily involving partial or complete duplication of organs comprising the gastrointestinal, genitourinary and distal neural tube systems. The term 'caudal duplication syndrome' was coined by Dominguez et al. in 1993, in a case series of six patients presenting with findings pertaining to duplication anomalies of genitourinary system, hindgut, lumbosacral spine and cord. We here report a unique case of caudal duplication presenting in late adolescence and briefly review the available literature on this rare abnormality.

Aerobic vaginitis - An underdiagnosed cause of vaginal discharge - Narrative review.

The concept of vaginal dysbiosis was for long considered synonymous with bacterial vaginosis (BV), which is characterized by a homogenous non-inflammatory vaginal discharge. The inflammatory variant of vaginal dysbiosis, called aerobic vaginitis (AV), has remained unknown to a large part of the global dermatology and venereology community, gynaecologists and reproductive tract infection specialists with consequential under diagnosis. AV significantly differs from BV, in clinical presentation, diagnostic criteria and management. The deleterious impact of untreated AV on pregnancy merits discussion. Understanding AV is also crucial for better comprehension of desquamative inflammatory vaginitis (DIV), the most severe form of the same entity. We review the condition's epidemiology, risk factors and suspected aetiology, symptoms and signs, and the latest evidence-backed approach to diagnosis and treatment. The ideal diagnostic approach and treatment for AV/DIV are yet to be established. The currently recommended diagnostic approach for AV/DIV merits an overhaul by incorporating changes to render it feasible for resource-constraint countries. The diagnostic criteria lack a uniform applicability in different physiological groups of women and cannot be used in postpartum or postmenopausal states at the same cut-off levels. Similarly, treatment guidelines merit a relook, and customization, given the equivocality of options suggested by different investigators.

Oral Tofacitinib: Contemporary Appraisal of Its Role in Dermatology.

Tofacitinib, an oral Janus kinase inhibitor (Jakinib), is an emerging treatment modality whose well-established efficacy in systemic inflammatory diseases is now being actively explored for cutaneous disorders (arising due to the patient's dysimmune responses) that are not responding to and/or sustaining intolerable adverse effects with the classical immunosuppressives and other targeted therapies such as the biologics. The most common dermatoses for which oral as well as topical Jakinibs such as tofacitinib have been evaluated and are being used albeit as an off-label indication include psoriasis, psoriatic arthritis, alopecia areata, vitiligo, and atopic dermatitis. This article provides a succinct review on the current status of oral tofacitinib in dermatology through literature search of PubMed database and stresses on the need for further evidence generation to define the drug's place in the therapeutic arsenal of dysimmune cutaneous disorders.

High accuracy theoretical investigations of CaF, SrF, and BaF and implications for laser-cooling.

The NL-eEDM collaboration is building an experimental setup to search for the permanent electric dipole moment of the electron in a slow beam of cold barium fluoride molecules [NL-eEDM Collaboration, Eur. Phys. J. D 72, 197 (2018)]. Knowledge of the molecular properties of BaF is thus needed to plan the measurements and, in particular, to determine the optimal laser-cooling scheme. Accurate and reliable theoretical predictions of these properties require the incorporation of both high-order correlation and relativistic effects in the calculations. In this work, theoretical investigations of the ground and lowest excited states of BaF and its lighter homologs, CaF and SrF, are carried out in the framework of the relativistic Fock-space coupled cluster and multireference configuration interaction methods. Using the calculated molecular properties, we determine the Franck-Condon factors (FCFs) for the A2Π1/2→X2Σ1/2 + transition, which was successfully used for cooling CaF and SrF and is now considered for BaF. For all three species, the FCFs are found to be highly diagonal. Calculations are also performed for the B2Σ1/2 +→X2Σ1/2 + transition recently exploited for laser-cooling of CaF; it is shown that this transition is not suitable for laser-cooling of BaF, due to the nondiagonal nature of the FCFs in this system. Special attention is given to the properties of the A'2Δ state, which in the case of BaF causes a leak channel, in contrast to CaF and SrF species where this state is energetically above the excited states used in laser-cooling. We also present the dipole moments of the ground and excited states of the three molecules and the transition dipole moments (TDMs) between the different states. Finally, using the calculated FCFs and TDMs, we determine that the A2Π1/2→X2Σ1/2 + transition is suitable for transverse cooling in BaF.

Extensive condylomata lata in an adolescent: An uncommon and unusual presentation.

Sexually transmitted infections (STIs) in children account for a great physical and psychosocial morbidity. Being rare, they require a high index of suspicion for diagnosis. STIs may also be the first indication of child sexual abuse (CSA). Consequences of an undetected infection are potentially devastating; conversely, a false suspicion can have equally detrimental effects on both the child and the parents. Herein, we report a case of acquired secondary syphilis in a child presenting with unusually extensive condylomata lata at multiple sites and review the literatue to understand the possible interrelationship of syphilis and CSA.

Tacalcitol: A useful adjunct to narrow band ultraviolet B phototherapy in psoriasis.

BACKGROUND: A combination of calcipotriol and narrow-band ultraviolet B (NBUVB) has been shown to have a superior efficacy as compared to NBUVB alone in psoriasis. Very few studies have been performed using the combination of NBUVB with tacalcitol, a comparatively newer Vitamin D analogue. OBJECTIVE: Comparison of the efficacy and safety of topical tacalcitol in combination with NBUVB versus NBUVB alone in psoriasis. METHODS: Thirty patients with plaque psoriasis were taken up for a 12 week, open-label, right-left intra-individual clinical trial. NBUVB phototherapy was given thrice weekly. The target lesions on one side were treated topically with tacalcitol ointment once daily, while no topical treatment was given on the other side. Efficacy was assessed by target plaque scoring. RESULTS: Better improvement in plaques was seen with combination therapy as compared to NBUVB monotherapy, with a statistically significant difference from 2 to 8 weeks. The combination led to an earlier clearance of plaques and a better maintenance of the response than NBUVB alone. The number of treatment sessions and cumulative NBUVB doses were significantly lower in the tacalcitol-treated group. CONCLUSION: Topical tacalcitol enhances the therapeutic effects of NBUVB therapy and exerts a UVB-sparing effect, without increasing the incidence of adverse effects.

Association of polymorphisms in angiotensin-converting enzyme gene with gestational diabetes mellitus in Indian women.

BACKGROUND: Numerous genes have been reported in relation with gestational diabetes mellitus (GDM), but the findings were not consistently replicated across populations, or there have been no detailed studies on them. Previous literatures suggested that, out of all angiotensin converting enzyme (ACE) gene polymorphisms, only ACE insertion/deletion (I/D) gene polymorphism has a strong association with GDM in Asian Indian women. AIM: This study was devoted to evaluate the association of four single nucleotide polymorphisms (SNPs) ACE A240T, C1237T, G2350A and I/D with GDM and Type 2 diabetes mellitus. MATERIALS AND METHODS: This study recruited 105 GDM cases, 119 Type 2 diabetes mellitus subjects and 120 controls. PCR-RFLP was used for identifying genotypes of ACE A240T, C1237T and G2350A and PCR was performed in the case of ACE I/D. RESULTS: Significant associations of ACE SNP's, C1237T, and G2350A with GDM were observed. Haplotype analysis revealed the remarkably significant evidence of association with SNP combination ACE A240T, C1237T, G2350A, and I/D with GDM patients (P = 0.024). Individuals possessing haplotype "TTAI" (frequency 30% in GDM and 0 in controls) derived from these SNPs had 185 fold increased risk of developing GDM (95% of confidence interval: 11.13-3102.15), which was highest when compared with other 15 haplotypes. CONCLUSION: Shorter-range haplotypes were also significant, but the only consistently associated alleles were found to be in ACE C1237T, G2350A, and I/D. These results suggested that the variant in close proximity to ACE C1237T, G2350A and/or I/D modulates susceptibility to GDM and noninsulin dependent diabetes mellitus in Indian women.

Recurrent first-trimester abortion in a young female: Rare presentation of Takayasu arteritis.

Takayasu arteritis (TA) is a chronic, progressive, autoimmune, idiopathic, and large-vessel vasculitis that usually affects young adults, especially females. TA primarily affects the aorta and its major branches, the coronary arteries, and the pulmonary arteries. Recurrent pregnancy loss is usually defined as three or more consecutive losses occurring at <20 weeks' gestation of a clinically recognized pregnancy. Common causes of recurrent fetal loss include anatomic, chromosomal, hormonal, infectious, or antiphospholipid antibody syndrome. However, to the best of our knowledge, TA causing recurrent fetal loss has not been described in the literature. We present such a rare case of a patient who presented with hemoptysis as her presenting complaint and also had a recurrent first-trimester abortion.

Cutaneous Metastasis from Signet-ring Gastric Adenocarcinoma in a Carcinoma En Cuirasse Pattern: An Unusual Clinical-diagnostic Sequence.

Cutaneous metastasis (CM) of gastric adenocarcinoma (ADC) is rare and usually presents late in the course of the disease. We report a rare case of carcinoma en cuirasse (CEC) pattern of CM secondary to gastric malignancy in a 55-year-old male patient-the interesting part being that CM was the first-presenting sign, which on further histopathological and immunohistochemical evaluation led to the diagnosis of hidden gastric carcinoma. The finding of signet ring cells (SRCs) on cutaneous biopsy further added a differential of the rare possibility of primary cutaneous tumors.

Harlequin syndrome: a mask of rare dysautonomic syndromes.

Harlequin syndrome (HS) is a rare disorder of the sympathetic nervous system which presents with unilateral decreased sweating and flushing of the face, neck, and chest in response to heat, exercise, or emotional factors. The contralateral side displays a compensatory overreaction to provide normal heat regulation of the face as a whole. In the literature, most of the cases are primary in nature and no underlying cause could be identified. Harlequin sign is used to denote these symptoms in patients who also exhibit associated oculosympathetic paresis, such as Horner syndrome, Adie syndrome, and Ross syndrome.We report a rare case of a 13-year-old boy who presented with complaints of flushing and sweating of the left side of the face after exertion, while the right side remained dry and maintained its normal color. No structural abnormality was identified on detailed work up. Thus, diagnosis of classic idiopathic HS was made. Despite the rarity of this syndrome, dermatologists should be acquainted with this distinctive entity and should refer the patient for complete ophthalmological and neurological examination.

Lyme disease in Haryana, India.

Lyme disease is a multiorgan animal-borne disease caused by the spirochete Borrelia burgdorferi. This case series highlights its presence in Haryana, a nonendemic zone. The first case was a 27-year-old housewife who presented with an annular erythematous patch with a central papule following an insect bite on the left upper arm. The second case was a 32-year-old farmer who gave a history of insect bite on the right arm followed by the development of an erythematous patch with a central blister. The third case, a 17-year-old boy presented with a history of tick bite over right thigh and a typical bull's eye lesion with central ulceration. These cases were managed with oral doxycycline 100 mg twice daily for 14 days. The fourth case was a 7-year-old boy with typical erythema migrans on the right check and neck while the fifth case, a 30-year-old housewife, presented with an erythematous patch with a central papule on the right buttock. These patients were treated with oral amoxycillin 25 mg/kg, thrice daily for 14 days. All patients showed IgM antibodies to B. burgdorferi. Treatment led to clearance of lesions in all the patients. Lyme borreliosis was diagnosed in these patients based on the history of established exposure to tick bites, presence of classic signs and symptoms, serology and the response to treatment.

Ectopic intraocular lens: an unusual complication of cataract surgery.

We wish to report an unusual complication of intraocular lens (IOL) insertion following uneventful phacoemulsification. After successful phacoemulsification surgery, a hydrophobic acrylic IOL was loaded in the injector for insertion into the capsular bag. During insertion, the IOL inadvertently extended into the corneal stromal lamella. The complication was recognized at a late stage, and the foldable acrylic lens was retrieved and reinserted correctly in the bag. The anterior chamber was made viscoelastically taut and was maintained in this state for 10 min, followed by a routine viscoelastic wash and air bubble injection. Cornea was slightly edematous with stromal haze, and the corneal thickness was 908 µm. At the 1-month follow-up visit, the patient's vision was 20/40, the stromal haze had subsided, the corneal thickness was 572 µm, and the patient was comfortable. Though it was unknown complication, following proper management patient recovered satisfactorily.