A [2.2]Isoindolinophanyl-Based Carbene (iPC) Ligand: Synthesis, Electronic and Photophysical Properties, and Application in Photocatalysis*.

Cyclic amino(alkyl) and cyclic amino(aryl) carbenes (cAACs/cAArCs) have been established as very useful ligands for catalytic and photonic applications of transition metal complexes. Herein, we describe the synthesis of a structurally related sterically demanding, electrophilic [2.2]isoindolinophanyl-based carbene (iPC) with a [2.2]paracyclophane moiety. The latter leads to more delocalized frontier orbitals and intense green fluorescence of (HiPC)OTf (2) from an intra-ligand charge transfer (1ILCT) state in the solid state. Base-promoted synthesis of the free carbene led to an unusual ring expansion and subsequent dimerization reaction, but the beneficial ligand properties can be exploited by trapping in situ at a metal center. The iPC ligand is a very potent π-chromophore, which participates in low energy metal-to-ligand (ML)CT transitions in [RhCl(CO)2(iPC)] (4) and IL-"through-space"-CT transitions in [Au(iPC)2]OTf (5). The steric demand of the iPC leads to high stability of 5 against air, moisture, or solvent attack, and ultralong-lived green phosphorescence with a lifetime of 185 µs is observed in solution. The beneficial photophysical and electronic properties of the iPC ligand, including a large accessible π surface area, were exploited by employing highly efficient energy transfer (EnT) photocatalysis in a [2+2] styrene cycloaddition reaction using 5, which outperformed other established photocatalysts in comparison.

First Three Years' Experience of Mucopolysaccharidosis Type-I Newborn Screening in California.

OBJECTIVE: To report on the first 3 years of mucopolysaccharidosis type I (MPS I) newborn screening (NBS) in the large and diverse state of California. STUDY DESIGN: The California Genetic Disease Screening Program began universal NBS for MPS I on August 29, 2018. The screening uses a 2-tiered approach: an α-L-iduronidase (IDUA) enzyme activity assay followed by DNA sequencing for variants in the IDUA gene. RESULTS: As of August 29, 2021, 1 295 515 California newborns were screened for MPS I. In tier 1 of screening, 329 (0.025%) had an IDUA enzyme measurement below the cutoff and underwent tier-2 IDUA DNA sequencing. After tier 2, 146 (0.011%) newborns were screen positive, all of whom were referred to a metabolic Special Care Center for follow-up. After long-term follow-up, 7 cases were resolved as severe MPS I (Hurler syndrome) and 2 cases as attenuated MPS I for an MPS I birth prevalence of 1/143 946. DNA sequencing identified 107 unique IDUA variants among a total of 524 variants; 65% were known pseudodeficiency alleles, 25% were variants of uncertain significance, and 10% were pathogenic variants. CONCLUSIONS: As a result of a 2-tiered NBS approach, 7 newborns diagnosed with Hurler syndrome had received early treatment for MPS I. Continuation of California's long-term follow-up program will be crucial for further understanding the complex genotype-phenotype relationships of MPS I.

Development and validation of a simple and robust method for arsenic speciation in human urine using HPLC/ICP-MS.

In order to better distinguish the different toxic inorganic and organic forms of arsenic (As) exposure in individuals, we have developed and validated a simple and robust analytical method for determining the following six As species in human urine: arsenous (III) acid (As-III), As (V) acid, monomethylarsonic acid, dimethylarsinic acid, arsenobetaine (AsB), and arsenocholine. In this method, human urine is diluted using a pH 5.8 buffer, separation is performed using an anion exchange column with isocratic HPLC, and detection is achieved using inductively coupled plasma-MS. The method uses a single mobile phase consisting of low concentrations of both phosphate buffer (5 mM) and ammonium nitrate salt (5 mM) at pH 9.0; this minimizes the column equilibration time and overcomes challenges with separation between AsB and As-III. In addition, As-III oxidation is prevented by degassing the sample preparation buffer at pH 5.8, degassing the mobile phase online at pH 9.0, and by the use of low temperature (-70 °C) and flip-cap airtight tubes for long term storage of samples. The method was validated using externally provided reference samples. Results were in agreement with target values at varying concentrations and successfully passed external performance test criteria. Internal QC samples were prepared and repeatedly analyzed to assess the method's long-term precision, and further analyses were completed on anonymous donor urine to assess the quality of the method's baseline separation. Results from analyses of external reference samples agreed with target values at varying concentrations, and results from precision studies yielded absolute CV values of 3-14% and recovery from 82 to 115% for the six As species. Analysis of anonymous donor urine confirmed the well-resolved baseline separation capabilities of the method for real participant samples.

Varying Course of External Branch of Superior Laryngeal Nerve (EBSLN) and Recurrent Laryngeal Nerve (RLN) in Thyroidectomy-An Observational Study.

Surgical management of a diseased thyroid depends on sonological and pathological evaluation and thereby, planning of the surgery. The definite surgery has two objectives: removal of the diseased gland and preservation of the nerves, namely EBSLN (External Branch of Superior Laryngeal Nerve) and RLN (Recurrent Laryngeal Nerve) and the Parathyroid glands. The objectives of the study were: (1) To identify the course of the RLN and EBSLN of both sides, during Thyroidectomy. (2) To discern various anatomical landmarks, the relations of the two nerves with them and anatomical variations, if any. In this Prospective observational study, fifty selected goitre patients underwent various types of thyroidectomies based on sonological and cytological criteria. The course and anatomical variations of EBSLN and RLN were photo-documented and results were analysed. Most of the EBSLN were found as Cernea type 1 type (25 out of 50), followed by Cernea type 2a (comprising 36%). The least common was type 2b. It was found that 36 out of 50 (72%) of RLN passed posterior to Inferior Thyroid Artery (ITA). Moreover, before piercing cricothyroid joint, the RLN showed bifurcation in 13 out of 50 subjects (26%), 1 participant had trifurcation and the remaining 36 (72%) had a single trunk. The EBSLN shows relation to the horizontal plane passing through the upper pole of the thyroid gland and it is more prone to get damaged when it passes within less than 1 cm to the plane. The RLN has various relations to the distinct anatomical landmarks thereby helping in safe dissection of the nerve. The study also noted the RLN in relation to ITA and branching before entering into the cricothyroid joint.

A spectroscopic investigation of a tridentate Cu-complex mimicking the tyrosine-histidine cross-link of cytochrome C oxidase.

Heme-copper oxidases have a crucial role in the energy transduction mechanism, catalyzing the reduction of dioxygen to water. The reduction of dioxygen takes place at the binuclear center, which contains heme a3 and CuB. The X-ray crystal structures have revealed that the C6' of tyrosine 244 (bovine heart numbering) is cross-linked to a nitrogen of histidine 240, a ligand to CuB. The role of the cross-linked tyrosine at the active site still remains unclear. In order to provide insight into the function of the cross-linked tyrosine, we have investigated the spectroscopic and electrochemical properties of chemical analogues of the CuB-His-Tyr site. The analogues, a tridentate histidine-phenol cross-linked ether ligand and the corresponding Cu-containing complex, were previously synthesized in our laboratory (White, K.; et al. Chem. Commun. 2007, 3252-3254). Spectrophotometric titrations of the ligand and the Cu-complex indicate a pKa of the phenolic proton of 8.8 and 7.7, respectively. These results are consistent with the cross-linked tyrosine playing a proton delivery role at the cytochrome c oxidase active site. The presence of the phenoxyl radical was investigated at low temperature using electron paramagnetic resonance (EPR) and Fourier transform infrared (FT-IR) difference spectroscopy. UV photolysis of the ligand, without bound copper, generated a narrow g=2.0047 signal, attributed to the phenoxyl radial. EPR spectra recorded before and after UV photolysis of the Cu-complex showed a g=2 signal characteristic of oxidized copper, suggesting that the copper is not spin-coupled to the phenoxyl radical. An EPR signal from the phenoxyl radical was not observed in the Cu-complex, either due to spin relaxation of the two unpaired electrons or to masking of the narrow phenoxyl radical signal by the strong copper contribution. Stable isotope (13C) labeling of the phenol ring (C1') Cu-complex, combined with photoinduced difference FT-IR spectroscopy, revealed bands at 1485 and 1483 cm(-1) in the 12C-minus-13C-isotope-edited spectra of the ligand and Cu-complex, respectively. These bands are attributed to the radical v7a stretching frequency and are shifted to 1468 and 1472 cm(-1), respectively, with 13C1' labeling. These results show that a radical is generated in both the ligand and the Cu-complex and support the unambiguous assignment of a vibrational band to the phenoxyl radical v7a stretching mode. These data are discussed with respect to a possible role of the cross-linked tyrosine radical in cytochrome c oxidase.

Synthesis and structural characterization of cross-linked histidine-phenol Cu(ii) complexes as cytochrome c oxidase active site models.

Tridentate cross-linked histidine-phenol Cu(ii) ether and ester complexes, chemical analogs of the active site of several heme-copper oxidases, have been synthesized and crystallized.

Estimation of partitioning of airflow in septal surgery: A prospective study with reference to the NOSE scale.

Improper patient selection for septal surgery often has been found to result in therapeutic failure, and there needs to be an objective assessment of nasal obstruction before the surgery and for postoperative follow-up that can be applied in the routine otolaryngology practice. The purpose of this study is to assess the usefulness of a cost-effective device for objective measurement of the nasal airway partitioning in selecting patients for septal surgery and for postoperative outcome evaluation. A hospital-based, prospective, observational study was carried out in a tertiary-care teaching institution involving 74 patients waiting for septal surgery. Each patient was exposed to subjective assessment of nasal obstruction by the Nasal Obstruction Symptom Evaluation (NOSE) scale and objective measurement by Nasal Partitioning Ratio (NPR) using a new device, Nasal Airway Partition Meter (NAPM), once before and twice after surgery. Overall, average NOSE score and NPR values were 66.42 ± 9.42 and 0.57 ± 0.18, respectively, at preoperative assessment (correlation coefficient 0.441). Sixty of the 74 patients had high values for both NPR and NOSE scores (Group 1), but in the remaining 14, NPR values were found to be lower despite high NOSE scores (Group 2). Postsurgery, the NOSE score and NPR values were significantly reduced in Group 1. In contrast, participants in Group 2 showed no alteration in the values of both the parameters after the same operative maneuver. However, 2 patients in Group 1 had NOSE score and NPR values unaltered, while 1 patient in Group 2 had a reduced NOSE score after surgery. Therefore, the validity of the new equipment was calculated to be 96.7% sensitive and 92.9% specific to identify patients who needed to undergo septal surgery for their nasal obstruction. It can be deduced from the present study that NAPM can be a cost-effective device for clinicians to objectively measure nasal airway obstruction and screen patients for septal surgery.

A new approach for studying fast biological reactions involving nitric oxide: generation of NO using photolabile ruthenium and manganese NO donors.

Nitric oxide (NO) is recognized as one of the major players in various biochemical processes, including blood pressure, neurotransmission and immune responses. However, experimental studies involving NO are often limited by difficulties associated with the use of NO gas, including its toxicity and precise control over NO concentration. Moreover, the reactions of NO with biological molecules, which frequently occur on time scales of microseconds or faster, are limited by the millisecond time scale of conventional stopped-flow techniques. Here we present a new approach for studying rapid biological reactions involving NO. The method is based on designed ruthenium and manganese nitrosyls, [Ru(PaPy3)(NO)](BF4)2 and [Mn(PaPy3)(NO)](ClO4) (PaPy3H = N,N-bis(2-pyridylmethyl)amine-N-ethyl-2-pyridine-2-carboxamide), which upon photolysis produce NO on a fast time scale. The kinetics of the binding of the photogenerated NO to reduced cytochrome c oxidase (CcO) and myoglobin (Mb) was investigated using time-resolved optical absorption spectroscopy. The NO was found to bind to reduced CcO with an apparent lifetime of 77 micros using the [Mn(PaPy3)(NO)]+ complex; the corresponding rate is 10-20 times faster than can be detected by conventional stopped-flow methods. Second-order rate constants of approximately 1 x 10(8) M(-1) s(-1) and approximately 3 x 10(7) M(-1) s(-1) were determined for NO binding to reduced CcO and Mb, respectively. The generation of NO by photolysis of these complexes circumvents the rate limitation of stopped-flow techniques and offers a novel alternative to study other fast biological reactions involving NO.

Postoperative hypofunctioning of the thyroid gland after total laryngectomy.

Primary laryngeal carcinoma is a common cancer, predominantly affecting males. Hypothyroidism is an undesirable sequela of both surgery and radiotherapy, the two most commonly used modalities of treatment. For advanced cases, standard treatment protocol includes total laryngectomy and neck dissection along with pre- or postoperative radiotherapy. Hemithyroidectomy is also routinely performed as an integral part of total laryngectomy. In the present study, assessment of the function of the remaining half of the thyroid gland has been done in cases of total laryngectomies in combination with uni- or bilateral neck dissection and pre- or postoperative radiotherapy. This prospective, observational study was carried out for a period of 5 years in the Otolaryngology Department of R.G. Kar Medical College and Hospital, Kolkata, India, involving a dynamic cohort of patients with advanced laryngeal carcinoma (stage T3 or T4a) who underwent total laryngectomy (including hemithyroidectomy) and bilateral or unilateral neck dissection for primary laryngeal cancer along with preoperative and postoperative radiotherapy. Assessment of the thyroid function was based on the measurement of serum thyroid-stimulating hormone and free thyroxine levels. The results revealed that 23.8%, 45.2%, and 73.8% patients developed either clinical or subclinical hypothyroid state at 6, 12, and 24 weeks, respectively, after the surgery. The estimation of relative risk (RR) was found to be most prominent among the group belonging to the "preoperative radiation with bilateral neck dissection" group at all levels of assessments, but all of the RRs were found to be insignificant per their 95% confidence intervals. Superiority of any method could not be established or refuted firmly due to the small sample size of the study. We presume that in the future, a study with a larger sample size, involving a meta-analysis of multicentric data, would be the most suitable method to throw some light on this issue.

Use of fluoroscopic guidance to remove a migrating esophageal foreign body.

Ingested foreign bodies that migrate extraluminally are rare. In such cases, exploration of the neck via an external approach is the recommended procedure to remove the object. However, locating such a foreign body can be a difficult task. We report what we believe is the first adult case of fluoroscopically guided localization of an accidentally ingested foreign body that had migrated into the soft tissues of the neck. We also review the other methods used to locate a migrating foreign body.

Unusual presentations of adenoid cystic carcinoma in extra-salivary gland subsites in head and neck region: a case series.

Adenoid cystic carcinoma (ACC) is an uncommon malignant epithelial tumor occurring in head neck region, accounting for approximately 10% of all salivary gland neoplasms. Extra-salivary gland involvement of other head neck subsites by ACC may present in unusual modes creating clinical dilemma. Here we present some cases with extra-salivary gland ACC. In this series six cases with extra-salivary gland ACC were included. Three patients presented with external auditory canal and temporo-mastoid region involvement of whom two cases also had intracranial extension. In one case tongue was the site of involvement where it was confused with benign neurogenic tumour. Palatal erosion with formation of oro-nasal fistula was the the manifestation of ACC involving palate. On the other hand sinonasal bleeding mass which came out as ACC on histopathological examination did not cause any palatal erosion and was removed successfully via lateral rhiniotomy. In all these cases patients were treated with post-operative radiotherapy and were closely followed up for early detection of any distant metastasis. The experience about the various unusual manifestations of ACC and the therapeutic challenge poised by the cases is discussed here.

Dysphagia due to forestier disease: three cases and systematic literature review.

Forestier disease or diffuse idiopathic skeletal hyperostosis (DISH) is an uncommon cause of dysphagia. Due to rarity of this condition there is neither any demographic data nor any consensus about the investigation and treatment modalities. Here an effort is made in the present article to compile the information regarding the demographic and clinical features, investigation modalities and different methods of treatment from all the available case reports of dysphagia due to Forestier disease in the English literature till date. Three cases of the same condition are also reported in the present paper. Three cases of dysphagia due to Forestier disease treated in the ENT department of R.G. Kar Medical College and Hospital are reported herewith. A systematic review of literature is also done. All the case reports of dysphagia due to Forestier disease are obtained by World Wide Web search (WWWS) using 'Forestier Disease', 'DISH' and 'dysphagia' as the key words. Data regarding age, sex, duration of the symptom, associated symptoms, investigations done, level of vertebrae involved and different modalities of treatment with result are collected and analyzed systematically. We found total 73 cases of dysphagia due to Forestier disease. The condition commonly affects males (M:F 5.64:1) in older age group (94.52% cases are 60 years or above), often presented to the treatment facility after a long time of initiation of the symptom. Barium swallow X-rays and lateral neck X-ray were the most common investigations done to arrive at a diagnosis as per result of systematic review. Surgical removal of the causative osteophytes were the definitive treatment, but if surgery is contraindicated, conservative measures like switchover to liquid and semisolid food and proper swallow training also improve the condition to some extent. Dysphagia due to Forestier disease mostly affects older male, often has a chronic course. It can be diagnosed with simple investigations like neck X-ray or barium swallow X-rays. The definitive treatment is surgical, but if contraindicated the problem can be palliated with simple measures like swallow training and change of food.

Migration of a fish bone from the upper aerodigestive tract to the skin of the neck: a case report.

We describe an unusual case of a migratory foreign body (fish bone) in the neck of a 45-year-old woman. The 2.1-cm bone migrated from the esophagus and traversed through the entire soft tissue of the neck, and it almost extruded through the skin of the neck. With the patient under local anesthesia, the foreign body was easily extracted through an incision over the skin.

Epidermoid cysts in head and neck: our experiences, with review of literature.

Epidermoid cysts are benign lesions, characterized by cystic spaces lined by simple squamous epithelium (epidermoid cyst), containing skin adnexa ("true" dermoid cyst) or tissues of all three germ layers (teratoid cyst). Head and neck constitute ~7% of all cases of epidermoid and dermoid cysts. There is often a diagnostic dilemma with the more common cystic lesions of this region. A retrospective case-series study of histologically proved epidermoid cysts in the head-neck region, from February 2008 to January 2011, in the Department of Otorhinolaryngology and Head-Neck Surgery of a tertiary Government teaching hospital in eastern India. The diagnosis was reached by fine needle aspiration cytology FNAC and subsequent histopathology where feasible. Necessary imaging was done for evaluation and management. A total of 28 cases were analyzed. 5 were female, with a male: female ratio of 4.6. Age range was from 2 to 60 years (mean = 30). Excision was the preferred treatment in 20 cases (71.4%). Various sites like the submandibular region (5), pinna (5), sublingual region (1), periorbital (6), suprasternal (6), along the anterior border of sternocleidomastoid (1) and glabella (3) were involved, along with an iatrogenic implantation epidermoid cyst in a tracheostomy scar. Some of the interesting cases presenting with clinical dilemma have been emphasized. Epidermoid cysts are relatively less common in the head-neck region, hence are liable to be misdiagnosed. In this case-series, few cases presenting with enough elements of confusion and dilemma are discussed with overall analysis and review of the related literature.

Modified technique of anterior nasal packing: a comparative study report.

Anterior nasal packing, which is a common procedure in otorhinolaryngology practice, has different complications. Pain during introduction and removal of pack, bleeding after removal due to mucosal damage and synechia formation are common among them. A continuous effort is going on worldwide to combat those by modifying the nature of pack material or inventing new materials for nasal packing. In the present study an effort was made to compare a new modification of conventional gauze pack by using aluminum foil prepared from the cover of suture materials as septal splint (to reduce the mucosal damage) with conventional gauze pack and another costly material, nasal tampon (merocel). Comparisons were done in terms of cost, efficacy and complications. Prospective hospital based interventional study. Patients were distributed into three groups according to the material used for anterior nasal packing. Comparisons were made in terms of cost of the material used, pain during introduction of pack, rise of systolic blood pressure, incidences of bleeding while pack in situ, incidences of bleeding after removal of pack that required repacking and incidences of synechia formation after pack removal. The episodes of bleeding while pack in situ, within first 48 h and forced for repacking was observed to be significantly more prevalent among nasal tampon groups (12.5%) of patients but only 2.1 and 2.4% with use of conventional gauze pack and our modification respectively. Regarding bleeding after removal of pack, 10.6% patients experienced bleeding with conventional gauze pack, whereas with our modification it was only 2.4%. Synechia formation was found to be highest among the cases with conventional gauze pack (14.9%), but with our modification it is only 2.4%. In this study it is found that use of aluminum foil prepared from the cover of suture materials can be very useful and cost effective method to reduce some of the complications of anterior nasal packing.

Glanzmann's Thrombasthenia: A Rare Cause of Recurrent Profuse Epistaxis.

Though epistaxis is a commonplace emergency encountered in the Otorhinolaryngology clinic, recurrent, severe and intractable cases are relatively less common. In those cases where no local causes are found that could explain such episodes, systemic causes, including hematological disorders should be considered, and thoroughly explored. However, routine hematological investigations often fail to identify a definite cause. Here we report about a 23 year-old woman presenting with severe recurrent epistaxis due to Glanzmann's thrombasthenia-a rare, autosomal recessive disease. Never before Glanzmann's thrombasthenia has been reported to present with severe epistaxis as its sole feature.

Atypical presentations of rhinosporidiosis: a clinical dilemma?

Rhinosporidiosis is a chronic inflammatory disease common in India and Sri Lanka. Its manifestations are mostly nasal, though extranasal ones in head and neck region are not rare. Occasionally these presentations lead to diagnostic dilemma. Here we present some cases with its associated confusions if any. In this study thirty five patients were included. Extranasal manifestations were noted in nine cases. Two patients attended with laryngopharyngeal and one with lacrimal sac presentation-subsequent nasal endoscopic examination revealed presence of nasal masses, too. Other six cases presented with polypoidal mass hanging from nasopharynx into oropharynx. One of them was confused with nasopharyngeal angiofibroma. Two laryngopharyngeal masses were removed successfully with rigid laryngoscope followed by cauterisation of the base. The solitary lacrimal sac mass was excised by external approach combined with nasal endoscope guided excision of nasal mass. The other six cases with nasopharyngeal attachment were subjected to nasal endoscope guided removal. In all these cases, the base of the lesions was cauterised. The experience about the various manifestations and diagnostic problems is discussed here.

Solitary neurilemmoma in postaural region.

Neurilemmoma in postaural region arising from great auricular nerve is an extremely rare tumour. An 11 years boy presented with pain and swelling behind his left ear for last 3-4 years. The clinical examination revealed the swelling appeared to be diffuse with the margin being ill defined. On radiological examination a diffuse homogeneous mass was seen in the postaural region of the left side. The tumour was completely removed by an incision through postaural route. Histopathological study revealed neurilemmoma. Postoperative period was uneventful.