A unifying model that explains the origins of human inverted copy number variants.

With the release of the telomere-to-telomere human genome sequence and the availability of both long-read sequencing and optical genome mapping techniques, the identification of copy number variants (CNVs) and other structural variants is providing new insights into human genetic disease. Different mechanisms have been proposed to account for the novel junctions in these complex architectures, including aberrant forms of DNA replication, non-allelic homologous recombination, and various pathways that repair DNA breaks. Here, we have focused on a set of structural variants that include an inverted segment and propose that they share a common initiating event: an inverted triplication with long, unstable palindromic junctions.

Template switching between the leading and lagging strands at replication forks generates inverted copy number variants through hairpin-capped extrachromosomal DNA.

Inherited and germ-line de novo copy number variants (CNVs) are increasingly found to be correlated with human developmental and cancerous phenotypes. Several models for template switching during replication have been proposed to explain the generation of these gross chromosomal rearrangements. We proposed a model of template switching (ODIRA-origin dependent inverted repeat amplification) in which simultaneous ligation of the leading and lagging strands at diverging replication forks could generate segmental inverted triplications through an extrachromosomal inverted circular intermediate.

Ribosomal DNA replication time coordinates completion of genome replication and anaphase in yeast.

Timely completion of genome replication is a prerequisite for mitosis, genome integrity, and cell survival. A challenge to this timely completion comes from the need to replicate the hundreds of untranscribed copies of rDNA that organisms maintain in addition to the copies required for ribosome biogenesis. Replication of these rDNA arrays is relegated to late S phase despite their large size, repetitive nature, and essentiality.

Comparison of Trocar Site versus Trocar Site Plus Intraperitoneal Instillation of Local Anesthetic for Shoulder Pain Following Laparoscopic Abdominal Surgery.

Background: Laparoscopic surgery in recent times has noteworthy advantages over conventional surgery, yet recovery is prolonged due to debilitating shoulder tip pain (STP) and operated site pain. Various studies have compared the effect of trocar site, intraperitoneal instillation of local anesthetic (LA) for pain relief while only a few studies have tested the combination of these two techniques. Hence, this study was undertaken to compare the combination of these two techniques versus trocar site alone for STP particularly.

Hydro-dissection of Dorsal Scapular Nerve for Neuropathy Post Radical Neck Dissection and Radiation: A Case Report.

Neuropathy of dorsal scapular nerve (DSN) following neck dissections or radiotherapy has not been reported so far nor has its treatment in the form of hydro-dissection. Hydro-dissection of nerve under ultrasound guidance has been receiving more attention in the recent past and it is a minimally invasive procedure. We report here a case of neuropathy of DSN following radiotherapy in a patient for whom we could at least provide pain relief as a palliative measure during his last 6 months of life.

Pulsed Radiofrequency of Stellate Ganglion for Neuropathic Pain Associated with Recurrent Pleural Leiomyosarcoma - A Case Report.

Pleural leiomyosarcomas are rare soft-tissue sarcomas. Neuropathic pain associated with such tumours can be quite debilitating. We present the case of a 62-year-old woman with chronic neuropathic pain refractory to pharmacologic interventions in association with recurrent pleural leiomyosarcoma.

Tumescent Local Anesthesia in Parotid Abscess - Novel Application of Old Technique.

Tumescent local anesthesia (TLA) is a regional anesthetic technique in which the diluted local anesthetic drug (commonly lidocaine) and epinephrine solution in large volume is injected subcutaneously around the site of incision. The main advantages of TLA are excellent bloodless field and longer duration of analgesia because of addition of epinephrine. Although TLA was used in various surgical procedures, there is no literature to date that has reported its use in the parotid region.

Comparison of Duration of Analgesic Comparison of Duration of Analgesic Effect of Nalbuphine and Morphine as an Adjuvant to Bupivacaine in the Supraclavicular Block under Ultrasound Guidance.

Background: Although many studies are available in the literature that has analyzed the effects of morphine, nalbuphine, and other opioids, no study had compared the effects of nalbuphine versus morphine as an adjuvant to bupivacaine in the supraclavicular block under the guidance of ultrasound.

Methodology: A randomized, double-blinded, prospective study was carried out on 60 patients of the American Society of Anesthesiologists Class I and II who were undergoing upper limb surgeries under the supraclavicular block. Patients were randomly allocated into two groups ( = 30).

The effects of manipulating levels of replication initiation factors on origin firing efficiency in yeast.

Chromosome replication in Saccharomyces cerevisiae is initiated from ~300 origins that are regulated by DNA sequence and by the limited abundance of six trans-acting initiation proteins (Sld2, Sld3, Dpb11, Dbf4, Sld7 and Cdc45). We set out to determine how the levels of individual factors contribute to time of origin activation and/or origin efficiency using induced depletion of single factors and overexpression of sets of multiple factors. Depletion of Sld2 or Sld3 slows growth and S phase progression, decreases origin efficiency across the genome and impairs viability as a result of incomplete replication of the rDNA.

Another simple regimen for perioperative management of diabetes mellitus.

Persons with diabetes who require surgical procedures are increasing day by day. Many of the regimens available to manage patients with diabetes perioperatively are complex. Hence, the junior doctors and the paramedics (Primary care providers on a 24/7 basis) find it difficult to execute them.

Phenotypic and Genotypic Consequences of CRISPR/Cas9 Editing of the Replication Origins in the rDNA of .

The complex structure and repetitive nature of eukaryotic ribosomal DNA (rDNA) is a challenge for genome assembly, thus the consequences of sequence variation in rDNA remain unexplored. However, renewed interest in the role that rDNA variation may play in diverse cellular functions, aside from ribosome production, highlights the need for a method that would permit genetic manipulation of the rDNA. Here, we describe a clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-based strategy to edit the rDNA locus in the budding yeast , developed independently but similar to one developed by others.

anti-inflammatory and skin protective properties of Virgin coconut oil.

Virgin coconut oil (VCO) has been traditionally used as moisturizer since centuries by people in the tropical region. Clinical studies have revealed that VCO improves the symptoms of skin disorders by moisturizing and soothing the skin. However, the mechanistic action of VCO and its benefits on skin has not been elucidated .

Comparative Evaluation of Ropivacaine and Ropivacaine with Dexamethasone in Transverse Abdominis Plane Block for Lower Abdominal Surgeries: A Prospective, Randomized, Double-Blinded Study.

Context: Dexamethasone as an adjunct to ropivacaine has shown promising results in prolonging the duration of analgesia in transverse abdominis plane (TAP) block. Only limited studies evaluated the effects of dexamethasone with ropivacaine in TAP block in specific population.

Aims: The effects of adding dexamethasone to ropivacaine on the quality and duration of TAP block in lower abdominal surgeries in multiple specialties were studied.

Efficacy of the Stellate Ganglion Block Through the Lateral Approach Using Ultrasonogram and Fluoroscopy.

Objective: Stellate ganglion (SG) block can provide pain relief in sympathetically mediated painful conditions. SG block at the sixth cervical (C6) vertebra level through lateral approach under the ultrasonogram (USG) guidance is very safe but may spare the fibres supplying the upper limb. When the drug is given at the C6 subfascially, it spreads along the cervical sympathetic chain, blocking the head/neck and upper limb.